To see the other types of publications on this topic, follow the link: PC paintbrush IV plus.
Journal articles on the topic 'PC paintbrush IV plus'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'PC paintbrush IV plus.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Socinski, Mark A., Igor Bondarenko, Nina A. Karaseva, Anatoly M. Makhson, Igor Vynnychenko, Isamu Okamoto, Jeremy K. Hon, et al. "Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial." Journal of Clinical Oncology 30, no. 17 (June 10, 2012): 2055–62. http://dx.doi.org/10.1200/jco.2011.39.5848.
Full textAbstract:
Purpose This phase III trial compared the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin with solvent-based paclitaxel (sb-paclitaxel) plus carboplatin in advanced non–small-cell lung cancer (NSCLC). Patients and Methods In all, 1,052 untreated patients with stage IIIB to IV NSCLC were randomly assigned 1:1 to receive 100 mg/m2 nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m2 sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC). The primary end point was objective overall response rate (ORR). Results On the basis of independent assessment, nab-PC demonstrated a significantly higher ORR than sb-PC (33% v 25%; response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P = .005) and in patients with squamous histology (41% v 24%; response rate ratio, 1.680; 95% CI, 1.271 to 2.221; P < .001). nab-PC was as effective as sb-PC in patients with nonsquamous histology (ORR, 26% v 25%; P = .808). There was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; hazard ratio [HR], 0.902; 95% CI, 0.767 to 1.060; P = .214) and overall survival (OS; median, 12.1 v 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; P = .271) in the nab-PC arm versus the sb-PC arm, respectively. Patients ≥ 70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC. Significantly less grade ≥ 3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the nab-PC arm, and less thrombocytopenia and anemia occurred in the sb-PC arm. Conclusion The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC.
2
Von Pawel, Joachim, Sang-We Kim, David R. Spigel, Christoph Zielinski, Maria Catherine Pietanza, Veerle de Pril, Marc S. Ballas, and Martin Reck. "CA184-156: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) plus etoposide/platinum (EP) versus placebo plus EP in patients (Pts) with newly diagnosed extensive-stage disease small cell lung cancer (ED-SCLC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): TPS7608. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.tps7608.
Full textAbstract:
TPS7608 Background: Phase III studies have not reported improvement for ED-SCLC beyond EP. Moreover, chemotherapeutic response in SCLC is short-lived, with a median survival of 8–12 months and 5-year survival rates ranging from 1%–2%. Ipi, a fully human monoclonal antibody which binds CTLA-4, augments antitumor immune responses and may potentially improve the clinical benefit of EP. A randomized phase II study of Ipi + paclitaxel/carboplatin (PC) in pts with ED-SCLC showed significant improvement in progression-free survival (PFS) [measured by immune-related response criteria (irRC)] over PC in pts receiving phased Ipi + PC; irRC were derived from WHO criteria to better capture response patterns observed with Ipi. Addition of Ipi trended toward prolonged overall survival (OS) and did not exacerbate PC toxicity; immune-related adverse events were managed using protocol-specific guidelines. This global (~227 sites among 34 countries), multicenter phase III study in pts with ED-SCLC (ClinicalTrials.gov identifier NCT01450761) will determine if adding Ipi to EP increases OS vs EP alone. Methods: Pts with first-line ED-SCLC and ECOG 0-1 will be eligible; pts with a history of autoimmune disease will be ineligible. Pts will be randomized (1:1 to either Arm A or Arm B) to 2 cycles of EP (etoposide [100 mg/m2, IV on Days 1-3 Q3W] and cisplatin [75 mg/m2, IV] or carboplatin [AUC=5, IV] once Q3W), followed by 4 cycles of blinded study drug (Ipi 10 mg/kg, IV in Arm A or placebo in Arm B, Q3W) with 2 concurrent cycles (during cycles 3-4) of EP and Ipi (6 cycles of total therapy). Eligible pts will receive Ipi maintenance therapy Q12W until disease progression or unacceptable toxicity; pts with a complete response will also be eligible for prophylactic cranial irradiation at investigator’s discretion. The primary endpoint is OS; secondary endpoints include OS among pts who receive blinded therapy, immune-related and mWHO PFS, best overall response rate, and duration of response. The trial will also characterize safety, and is estimated to enroll 1100 pts. Clinical trial information: NCT01450761.
3
Conte, P. F., M. Bruzzone, S. Chiara, M. R. Sertoli, M. G. Daga, A. Rubagotti, A. Conio, et al. "A Randomized Trial Comparing Cisplatin Plus Cyclophosphamide Versus Cisplatin, Doxorubicin, and Cyclophosphamide in Advanced Ovarian Cancer." Journal of Clinical Oncology 4, no. 8 (August 1986): 1284. http://dx.doi.org/10.1200/jco.1986.4.8.1284.
Full textAbstract:
In the article by Conte et al, "A Randomized Trial Comparing Cisplatin Plus Cyclophosphamide Versus Cisplatin, Doxorubicin, and Cyclophosphamide in Advanced Ovarian Cancer" (Journal of Clinical Oncology 4:965–971, 1986), an error was made in the abstract on page 965 that altered the meaning of a sentence. The correct sentence appears below. After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) or PAC (PC + doxorubicin 45 mg/m2).
4
Ruiz, Rolando, and Carolyn Behrendt. "Venous thromboembolism among patients with advanced lung cancer randomized to prinomastat or placebo, plus chemotherapy." Thrombosis and Haemostasis 90, no. 10 (2003): 734–37. http://dx.doi.org/10.1160/th03-01-0041.
Full textAbstract:
SummaryTwo clinical trials have suggested that the combination of vascular endothelial growth factor inhibitor with chemotherapy is associated with venous thromboembolism (VTE). This retrospective cohort study investigates whether a similar association exists when matrix metalloproteinase inhibitor (prinomastat) is combined with chemotherapy.Patients (n=1,023) with stage IIIB, IV, or recurrent non-small cell lung cancer (NSCLC) were followed during 2 randomized, double-blind trials of prinomastat versus placebo orally bid, plus gemcitabine/cisplatin (GC) or paclitaxel/carboplatin (PC). VTE included deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed by imaging or autopsy. Risks identified in univariate analysis (incidence densities compared by t test) were confirmed in multivariate analysis (proportional hazards model).During 7,500.3 patient-months, 58 VTE (31 PE, 27 isolated DVT) were confirmed in 54 patients. On univariate analysis, VTE was associated with central venous catheter placed within 3 months,15 mg prinomastat plus GC, and to a lesser extent, 15 mg prinomastat plus PC, baseline performance status, and histologic type. VTE incidence was not increased by 15 mg prinomastat alone (post-discontinuation of chemotherapy), by chemotherapy plus placebo, or by 5 or 10 mg prinomastat plus chemotherapy. On multivariate analysis, VTE hazards (95% confidence interval) were 5.69 (2.61, 12.40) with recently placed central catheter, 2.78 (1.42, 5.43) with 15 mg prinomastat plus GC, and 2.06 (0.98, 4.31) with 15 mg prinomastat plus PC; performance status and histology were nonsignificant.We can conclude that combined treatment with 15 mg prinomastat plus chemotherapy approximately doubles the hazard of VTE among patients with advanced NSCLC.Research support: Pfizer Inc
5
Perez, Kimberly, James M. Cleary, Thomas Benjamin Karasic, Srivatsan Raghavan, Osama E. Rahma, Jonathan Nowak, Erkut Hasan Borazanci, et al. "Vitamin D receptor agonist paricalcitol plus gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): TPS784. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.tps784.
Full textAbstract:
TPS784 Background: Patients(pts) with metastatic pancreatic cancer (PC) have a median survival of less than one year even with use of multiagent chemotherapy programs. Pancreatic tumors are composed of multiple cell types and a dense extracellular matrix that may support cancer cell proliferation and impede chemotherapy delivery. Cancer-associated fibroblasts (CAF’s) in the tumor microenvironment secrete pro-inflammatory factors and components of the extracellular matrix. In PC laboratory models, engagement of the vitamin D receptor (VDR) by VDR agonists shifts CAFs toward a more quiescent phenotype with reduced tumor growth and improved chemotherapy penetration (Sherman. Cell, 2014). Paricalcitol is a synthetic VDR agonist used in patients with secondary hyperparathyroidism due to chronic kidney disease. A prior pilot study evaluated IV paricalcitol with gemcitabine (G) and nab-paclitaxel (A) before surgical resection in patients with resectable PC (NCT02030860). Methods: Pts with previously-untreated metastatic PC will be enrolled in a two-stage study consisting of a safety run-in and a randomized phase 2 study (NCT03520790). In the run-in stage, 36 pts will be randomized 1:1:1 to G (1000 mg/m2) and A (125 mg/m2) given 3 weeks on and 1 week off plus: (a) paricalcitol 25mcg IV thrice weekly, (b) paricalcitol 16mcg oral daily, or (c) placebo oral daily. Grade 3/4 hypercalcemia or genitourinary stones will be considered dose limiting toxicities.Pts will undergo paired pre- and on-treatment tumor biopsies to examine pharmacodynamic (PD) markers by bulk and single cell RNA sequencing and multiplex immunofluoresence.Assuming safety and supportive PD assessments, the phase 2 study will randomize an additional 76 pts to two treatment arms with GA plus: (a) paricalcitol or (b) placebo.Paricalcitol formulation (IV or oral) will be determined based on data from the run-in stage.The primary endpoint of the phase 2 study is overall survival, with a total of 100 pts needed to identify a hazard ratio of 0.6 with 80% power and one-sided alpha of 0.10.Secondary endpoints include safety, response rate, and progression free survival.Trial funding provided by SU2C, CRUK,Lustgarten Foundation, and AACR. Clinical trial information: NCT03520790.
6
Agarwala, S. S., U. Keilholz, D. Hogg, C. Robert, P. Hersey, A. Eggermont, S. Grabbe, R. Gonzalez, K. Patel, and A. Hauschild. "Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 8510. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8510.
Full textAbstract:
8510 Background: Sorafenib (SOR), a potent and selective multi-kinase inhibitor, exerts its anti-tumor and anti-angiogenic effects via inhibition of VEGFR-1, -2, -3, PDGFR-a, -β, and Raf. Promising results from a single-arm study of paclitaxel and carboplatin plus sorafenib (PC+SOR) in advanced melanoma warranted further investigation in a randomized phase III trial. Methods: Eligibility criteria: measurable disease by RECIST, progressive disease (PD) on dacarbazine or temozolomide-containing regimen. Prior adjuvant immunotherapy was allowed; pts with active brain metastases were excluded. Pts stratified by stage (unresectable III vs IV, M1a/M1b vs M1c) and ECOG PS (0 vs 1) were randomized to receive P 225 mg/m2 and C AUC=6 on day 1 every 3 wks + oral placebo (PL) or oral SOR 400 mg bid on Days 2–19 every 3 wks until the occurrence of PD or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Using a two-sided test with a = 0.01, 173 PFS events were needed to detect a hazard ratio (HR) of 0.56 (SOR/PL) with 90% power. The secondary endpoints were overall survival, objective response rate (ORR) and time to progression. Results: 270 pts randomized over 12 mos in equally balanced groups had: median age 57 yrs, male 63%, ECOG PS 1 46%, Stage IV M1c 69% and elevated LDH 46%. At the time of analysis by independent assessment, the median PFS of PC+PL vs PC+SOR was 17.9 wks (99% CI: 11.3, 22.9) vs 17.4 wks (99% CI: 11.9, 23.1), HR 0.906 [p=0.492]; PFS rate at Day 180 was 29% vs 32%, ORR was 11% vs 12%. Both regimens were well-tolerated with the following selected = Grade 3 toxicities in PC+PL vs PC+SOR: neutropenia (46% vs 49%), febrile neutropenia (7% vs 9%), thrombocytopenia (12% vs 28%), sensory neuropathy (13% vs. 20%), thrombosis/embolism (6% vs 4%), rash/desquamation (0 vs 7%), hand-foot skin reaction (0 vs 7%), fatigue (10% vs 16%), diarrhea (3% vs 8%) and hemorrhage (3% vs 2%). There were 2 deaths, possibly related to treatment with PC+SOR. Conclusions: The addition of SOR to PC did not improve PFS or ORR in this second-line patient population. Toxicity of PC+SOR is tolerable. The utility of PC+SOR in chemotherapy-naïve advanced melanoma pts remains an important question and a phase III trial is currently in progress (E2603). [Table: see text]
7
Choy, Hak, Lee Steven Schwartzberg, Shaker R. Dakhil, Edward B. Garon, Janak K. Choksi, Ramaswamy Govindan, Guangbin Peng, Andrew Koustenis, Joseph Treat, and Coleman K. Obasaju. "Phase II study of pemetrexed (P) plus carboplatin (Cb) or cisplatin (C) with concurrent radiation therapy followed by pemetrexed consolidation in patients (pts) with favorable-prognosis inoperable stage IIIA/B non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 7002. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7002.
Full textAbstract:
7002 Background: There is no consensus chemotherapy regimen with concurrent radiation therapy (CRT) for inoperable stage IIIA/B NSCLC. P synergizes with ionizing radiation, as well as with Cb and C in preclinical models. These doublets have shown efficacy and favorable toxicity profiles in phase II/III trials. Methods: In this open-label randomized phase II trial, 98pts with inoperable stage IIIA/B NSCLC (all histologies) were randomized (1:1) to P 500 mg/m2 plus Cb AUC 5 (PCb) or P 500 mg/m2 plus C 75 mg/m2 (PC) intravenously (IV) every 21 days for 3 cycles. All pts received CRT 64–68 Gy (2 Gy/day, 5 days/week, Days 1–45). Consolidation P 500 mg/m2 IV every 21 days for 3 cycles began 3 weeks after completion of CRT. The primary endpoint was 2-year overall survival (OS); secondary endpoints included median OS, time to progression (TTP), overall response rate (ORR), and toxicity. Results: Since Jun 2007, 98 pts were enrolled (PCb: 46; PC: 52).Pts were followed until Oct 2011. Mean dose compliance was PCb: 95.7% P, 97.1% Cb; PC: 89.7% P, 89.1% C. Mean dose compliance for CRT was PCb: 95.7%; PC: 88.1%. CRT dose interruptions occurred in PCb: 32.6% and PC: 40.4%. Two-year OS was PCb: 45.2% (95% confidence interval [CI], 29.3-59.8); PC: 57.6% (95% CI, 41.6-70.7); p=0.270. Median OS (months) was PCb: 18.7 (95% CI, 12.9-not assessable [N/A]); PC: 27.0 (95% CI, 23.2-N/A). Median TTP (months) was PCb: 8.8 (95% CI, 6.0-10.7); PC: 13.1 (95% CI, 8.3-N/A); p=0.057. The ORR rates were PCb: 52.2% (complete response [CR], 6.5%; partial response [PR], 45.7%); PC: 46.2% (CR, 3.8%; PR, 42.3%). Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. No drug-related deaths were reported. Conclusions: While conclusions are limited by the size of the trial, this study suggests OS and TTP advantages for the C-containing arm. Both combinations with CRT appear well tolerated.
8
Powell, Matthew A., Virginia L. Filiaci, Martee Leigh Hensley, Helen Q. Huang, Kathleen N. Moore, Krishnansu Sujata Tewari, Larry J. Copeland, et al. "A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG Oncology trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5500. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5500.
Full textAbstract:
5500 Background: Gynecologic carcinosarcomas (CS) are rare yet aggressive epithelial malignancies for which optimal therapy is debated. PI was shown to be superior to I. PC demonstrated compelling phase 2 activity with improved safety and convenience. Methods: Main inclusion: ≥18 y; chemotherapy naïve stage I-IVB or recurrent uterine (U) or ovarian (O) CS. Treatment randomised 1:1 to PC (P 175mg/m2 with C: AUC 6 or 5 if prior RT on D1) or PI (P: 135 mg/m2; I 1.6 g/m2 D1-3; G-CSF support with dose escalation & de-escalation based on nadir counts) q21days for 6-10 cycles. Quality of life (QOL) (FACT-En TOI) and neurotoxicity (FACT/GOG-Ntx subscale) administered at 4 timepoints. A stratified log-rank test compared primary endpoint of overall survival (OS) from entry between treatment groups for non-inferiority (NI) of PC to PI. With 264 events, power was 80% for a null hazard ratio of 1.2 against a 13% greater death rate on PI when type I error is limited to 5% for a one-tail test. NCT00954174. Results: 637 pts accrued with a median follow-up of 61 months. The primary (U, n = 536) and secondary (O, n = 101) cohorts are analyzed separately and included 449 and 90 pts eligible pts, respectively. For the U cohort:PC and PI were randomly assigned to 228 and 221 eligible pts. Stage distribution: I (40%), II (6%), III (31%), IV (15%) and recurrent (8%). The study met its primary objective withPC not inferior to PI (intention-to-treat analysis;Median OS 37 vs. 29 mo, HR = 0.87; 90% CI = 0.70 to 1.075; p < 0.01 for NI, p > 0.1 for superiority (S)).PFS (median on PC 16mo vs PI 12mo; HR = 0.73; p = < 0.01 for NI, p < 0.01 for S). Toxicity (grade 1/2/3/4/5: PC 1/8/40/48/2%; PI 1/32/39/25/1%). Most of increase toxicity for PC was hematologic with G-CSF rarely used (N = 6). Confusion and genitourinary hemorrhage were significantly worse with PI. Both groups had decline in QOL and neurotoxicity scores. Similar trends were noted for the O cohort (OS: PC 30mo vs PI 25mo; and PFS: 15 mo vs 10 respectively). Conclusions: PC was not inferior to PI for OS with longer PFS and similar QOL and neurotoxicity. These results establish a new standard regimen for women with CS. Clinical trial information: NCT00954174.
9
Tomlinson, Ben Kent, John S. Bomalaski, Monica Diaz, Taiwo Akande, Nichole Mahaffey, Tianhong Li, Mrinal P. Dutia, et al. "Phase I trial of ADI-peg 20 plus docetaxel (DOC) in patients (pts) with advanced solid tumors." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 2569. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2569.
Full textAbstract:
2569 Background: ADI-PEG20 is an enzyme that degrades arginine (Arg), an amino acid relevant to biosynthetic pathways of normal and malignant cells. It has shown tolerability and activity in several solid tumors. Preclinical studies have shown that Arg deprivation by ADI-PEG 20 in cancer cells induces autophagy, caspase-independent apoptosis, and potentiates DOC-induced cytotoxicity in prostate cancer (PC) models. A phase I trial (standard 3+3 design) of ADI-PEG20 (IM weekly) plus DOC (IV on day 1 q 3 weeks) was conducted to assess feasibility and safety of the combination. Methods: Eligible pts were >18 years of age, had advanced malignant solid tumors, adequate end organ function, and performance status (PS) 0-2. ADI-PEG 20 was escalated over 4 dose levels (4.5, 9, 18, 36 mg/m2). DOC dose was 75 mg/m2. Dose limiting toxicity (DLT) was defined as any of the following in cycle 1: thrombocytopenia [grade (Gr) 3 with bleeding/transfusion, or Gr 4]; neutropenia with fever or documented infection attributable to ADI PEG20; or any ≥ Gr 3 non-heme toxicity related to study drug except alopecia. Allergic reaction associated with DOC was not considered a DLT. Serum levels of Arg were serially measured. Results: 18 pts were accrued: median age, 64.5 yrs; male, 83%; PS 0, 72%. Most common tumors were NSCLC (8), PC (3), and tongue cancer (TC) (2). Median number of prior systemic therapies was 3. One DLT was seen in dose level 1 (urticarial rash) requiring expansion of that dose level to 6 pts. No additional DLTs attributable to ADI PEG20 were seen. Serious adverse events (all expected and attributed to DOC) were recorded in 11/18 pts, including Gr IV neutropenia (6, 33%) and Gr IV anemia (2, 11%). There were 2 on-study deaths unrelated to protocol therapy. In 11 pts with evaluable disease, 1 with TC had a partial response (PR), 6 had stable disease (SD) (3 NSCLC, 2 PC, 1 TC). Arg levels decreased in the 1st cycle for 6/11 pts with available data, including 2 with SD, and 1 with PR. Conclusions: The combination of ADI PEG20 and DOC is feasible with reasonable tolerability in this heavily pre-treated cohort. Full doses of both agents were achievable: ADI-PEG 20 at 36mg/m2 with DOC 75 mg/m2. An expansion cohort of castration resistant PC pts is now accruing at this recommended dose. Clinical trial information: NCT01497925.
10
Conte, P. F., M. Bruzzone, S. Chiara, M. R. Sertoli, M. G. Daga, A. Rubagotti, A. Conio, M. Ruvolo, R. Rosso, and L. Santi. "A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer." Journal of Clinical Oncology 4, no. 6 (June 1986): 965–71. http://dx.doi.org/10.1200/jco.1986.4.6.965.
Full textAbstract:
After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.
11
Wang, Hui, Shaoyu Mou, and Min Tu. "Study on the Effect of Nano Albumin Paclitaxel Combined with Carboplatin in the Treatment of Lung Squamous Cell Carcinoma." Journal of Nanoscience and Nanotechnology 20, no. 12 (December 1, 2020): 7439–43. http://dx.doi.org/10.1166/jnn.2020.18880.
Full textAbstract:
This study aims to compare the efficacy and side effects of albumin-binding paclitaxel plus carboplatin (NAB PC) and paclitaxel plus carboplatin (PC) in the first-line treatment of advanced non-small cell lung cancer (NSCLC). A total of 60 patients with advanced NSCLC diagnosed by histopathology or cytology were randomly divided into nab PC group (albumin-binding paclitaxel 130 mg/mL, D1, D; carboplatin AUC = 6, D1) and PC group (paclitaxel 175 mg/mL, D1; carboplatin AUC = 6, D1), one cycle every three weeks. RECIST 1.1 standard was used to evaluate the short-term objective efficacy, and who acute and subacute toxicity classification standard was used to evaluate the toxicity. The total effective rate (RR) and disease control rate (DCR) of NAB PC group were 40.0% and 80.0%, respectively, which were higher than 23.3% and 60.0% of the PC group, respectively. This difference was statistically significant (p < 0.05). In squamous cell carcinoma, the RR of NAB PC group and PC group were 57.1% (8/14) and 23.1% (3/13) respectively, with a statistically significant difference (p < 0.05); in non-squamous cell carcinoma, the RR of the two groups were 25.0% (4/16) and 23.3% (4/17) without statistical significance (p > 0.05). The median progression free survival time of the NAB PC group and PC group was 6.5 and 5.9 months, respectively, with no significant difference (p>0.05). No significant difference arose in the incidence of grade III–IV toxicity between the two groups (p > 0.05). The incidence of neutropenia in the NAB PC group was higher than that in the PC group (p < 0.05). The therapeutic effect of paclitaxel combined with carboplatin in the treatment of advanced NSCLC is better, the effect of paclitaxel combined with carboplatin is better, and the side effects can be tolerated, which is worthy of clinical application. Patients are more satisfied with their care.
12
Dolma, Tshering, Reena Mukherjee, B. K. Pati, and U. K. De. "Acute Phase Response and Neutrophils : Lymphocyte Ratio in Response to Astaxanthin in Staphylococcal Mice Mastitis Model." Journal of Veterinary Medicine 2014 (November 19, 2014): 1–5. http://dx.doi.org/10.1155/2014/147652.
Full textAbstract:
The purpose of the study was to determine the immunotherapeutic effect of astaxanthin (AX) on total clinical score (TCS), C-reactive protein (CRP), and neutrophil : lymphocyte ratio in mice mastitis model challenged with pathogenic Staphylococcus aureus. Twenty-four lactating mice were divided in 4 equal groups: group I mice served as normal healthy control, group II, positive control, were challenged with pathogenic S. aureus, group III mice were challenged and treated with AX, and group IV were treated with amoxicillin plus sulbactum. The TCS was higher in postchallenged mice; however it was significantly higher in group II untreated mice as compared to group III and group IV mice. The neutrophil was higher and lymphocyte count was lower in group II mice at 120 hrs post challenge (PC). The CRP was positive in all the challenged group at 24 hrs PC, but it remained positive till 120 hrs PC in group II. The parameters are related to enhancement of the mammary defense and reduction of inflammation. Hence AX may be used alone or as an adjunct therapy with antibiotic for amelioration of mastitis. Development of such therapy may be useful to reduce the antibiotic burden in management of intramammary infection.
13
Tauchi, Junko, Akira Shinohara, Ken Ohashi, Taro Shibuki, Gen Kimura, Kumiko Umemoto, Kazuo Watanabe, et al. "Impact of glycemic control on treatment efficacy and safety during nabpaclitaxel plus gemcitabine therapy in unresectable pancreatic cancer." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 337. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.337.
Full textAbstract:
337 Background: Diabetes mellitus (DM) and hyperglycemia have been widely considered to be associated with the risk of pancreatic cancer. However, the aim of this study was to evaluate the relationship between glycemic control and the efficacy or safety in pancreatic cancer pts receiving treatment with nab-Paclitaxel (nab-PTX) plus Gemcitabine (GEM). Methods: We retrospectively reviewed 285 pts with unresectable pancreatic cancer with nab-PTX plus GEM as the first-line chemotherapy from December 2014 to March 2017 at the National Cancer Center Hospital East, Kashiwa, Japan. The pts were divided into two groups, average blood glucose level during the period of chemotherapy was less than 160 mg/dL (Group GC: Good glycemic control group) and more than 160 mg/dL (Group PC: Poor glycemic control group). Results: A total of 285 pts were enrolled. Median age was 66 years (range: 26-84) and males/females: 180/105, PS (0-1/2-3): 272/13, stage (III/IV): 77/208. There were 226 pts in GC group and 59 pts in PC group. No significant differences were seen in the overall survival between Group GC and PC (median: 16.1 months vs. 13.8 months, p = 0.344) and in the progression free survival between the two groups (median: 7.5 months vs. 8.2 months, p = 0.862). The incidence rate of grade 2-3 chemotherapy-induced peripheral neuropathy (CIPN) was significantly higher in Group PC compared with Group GC (Group GC 28.3%, Group PC 45.8%, p = 0.010). Univariate and multivariate analyses identified glycemic control as significant independent factors associated with the incidence of grade 2-3 of CIPN (Odds ratio 2.182, 95% CI 1.20-3.96, p = 0.010). There was no significant difference in the relative dose intensity of nab-PTX between two groups (median, 56.6% in group GC, 56.5% in group PC, p = 0.952). Conclusions: Glycemic control during the chemotherapy with nab-PTX plus GEM in unresectable pancreatic cancer was not associated with OS. The incidence of severe CIPN was higher in pts with poor glycemic control compared with good glycemic control.
14
Spigel, David R., Christoph Zielinski, Sabine Maier, Veerle de Pril, Justin P. Fairchild, Jean-Marie Cuillerot, and Martin Reck. "CA184-156: A randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) plus etoposide/platinum (EP) versus EP in subjects with newly diagnosed extensive-stage disease small cell lung cancer (ED-SCLC)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): TPS7113. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps7113.
Full textAbstract:
TPS7113 Background: EP (4-6 cycles) is standard of care 1st-line therapy for metastatic SCLC, and no multinational studies have reported any improvement beyond that reported for EP. Evidence of an ongoing immune response to SCLC tumors suggests that immunotherapy that enhances this immune response to SCLC may enhance the clinical benefit of EP. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Because some responses to Ipi may differ from those observed with cytotoxic therapies, immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi with paclitaxel/carboplatin (PC) in pts with ED-SCLC showed significant improvement in progression-free survival (PFS), as measured by irRC, over PC alone in pts receiving Ipi and PC in a phased regimen (Ipi started after 2 cycles of PC). Furthermore, addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. This multicenter phase III study in pts with ED-SCLC (ClinicalTrials.gov identifier NCT01450761) will determine whether adding Ipi to EP increases OS vs EP alone. Methods: EP consists of 4 cycles of etoposide (100 mg/m2, IV on Days 1-3 every 3 weeks [Q3W]) and cisplatin (75 mg/m2, IV) or carboplatin (AUC=5, IV) once Q3W. Pts will be randomized to receive 4 doses of Ipi (10 mg/kg, IV) in Arm A or placebo in Arm B, Q3W during induction, starting after 2 cycles of EP (phased schedule). Eligible pts will then receive blinded study drug (Ipi in Arm A; placebo in Arm B) Q12W until disease progression or unacceptable toxicity. The primary objective is to compare OS. Secondary objectives are to compare OS in those who receive blinded study drug, compare PFS between study arms, and to estimate best overall response rate and duration of response. First-line ED-SCLC pts with ECOG performance ≤1 will be included. Pts with symptomatic CNS metastases or a history of autoimmune disease will be excluded. The study will randomize 1100 pts at a 1:1 ratio.
15
Aisuodionoe-Shadrach, Oseremen, and Sadiq N. Abu. "Incidence of Skeletal-Related Events in Patients With Advanced and Metastatic Prostate Cancer Treated With Hormone Therapy in a Low- and Middle-Income Country." Journal of Global Oncology 3, no. 2_suppl (April 2017): 41s. http://dx.doi.org/10.1200/jgo.2017.009209.
Full textAbstract:
Abstract 16 Background: Skeletal-related events (SREs) are fractures, radiotherapy to bone, or spinal cord compression that occurs concurrently with or after the first bone metastasis in men with prostate cancer (PC) and may result from hormone therapy (HT). In this work, we report the incidence of SREs in patients with PC who are treated with HT and highlight the burden of advanced and metastatic PC in a practice in a low- and middle-income country. Methods: Retrospective data was of newly diagnosed patients with PC with SREs who were treated with androgen deprivation therapy at the University of Abuja Teaching Hospital, Abuja, Nigeria, between January 2012 and December 2015. Results: Of 219 cases reviewed, 142 patients (64.8%) had American Joint Committee on Cancer stage IV PC and so commenced treatment with HT, with > 50% of these patients being older than 65 years (mean [standard deviation], 68.3 [± 9.5] years). Serum prostate-specific antigen range was 1.4 to 2,461.58 ng/mL (mean [standard deviation], 113.7 [± 288.9] ng/mL). Twenty-nine patients (20.5%) had one or more SREs: spinal cord compression (19.1%), pathological fractures (1.4%), and radiotherapy to the affected bone (1.4%) being the most common. Fifty additional patients (35.2%) had bone pain with localization to the lumbosacral spine in > 50% of them, whereas two patients with pathologic fractures had internal fixation and bone radiotherapy, respectively. HT was orchiectomy, luteinizing hormone-releasing hormone agonists (LHRH), antiandrogens, and complete androgen blockade (orchiectomy plus antiandrogens) in 14 (9.8%), 3 (2.1%), 44 (30.9%), and 81 (57%) patients, respectively. Conclusion: That 65% of our patients had advanced or metastatic PC at first diagnosis lends credence to late presentation with increased morbidity and mortality of PC in our environment where penetration of radiotherapy services and access to LHRH is significantly low, as evidenced by patients who had complete androgen blockade that was treated with orchiectomy plus antiandrogens. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from either author.
16
Arrieta, Oscar, Claudia H. González-De la Rosa, Elena Aréchaga-Ocampo, Geraldine Villanueva-Rodríguez, Tania L. Cerón-Lizárraga, Luis Martínez-Barrera, María E. Vázquez-Manríquez, et al. "Randomized Phase II Trial of All-Trans-Retinoic Acid With Chemotherapy Based on Paclitaxel and Cisplatin As First-Line Treatment in Patients With Advanced Non–Small-Cell Lung Cancer." Journal of Clinical Oncology 28, no. 21 (July 20, 2010): 3463–71. http://dx.doi.org/10.1200/jco.2009.26.6452.
Full textAbstract:
Purpose This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel (PC) plus all-trans retinoic acid (ATRA) increases response rate (RR) and progression-free survival (PFS) in patients with advanced non–small-cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of retinoic acid receptor beta 2 (RAR-β2) as a response biomarker. Patients and Methods Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m2/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-β2 expression was analyzed in tumor and adjacent lung tissue. Results One hundred seven patients were included, 55 in the P/PC group and 52 in the RA/PC group. RR for RA/PC was 55.8% (95% CI, 46.6% to 64.9%) and for P/PC, 25.4% (95% CI, 21.3 to 29.5%; P = .001). The RA/PC group had a longer median PFS (8.9 v 6.0 months; P = .008). Multivariate analysis of PFS showed significant differences for the RA/PC group (hazard ratio, 0.62; 95% CI, 0.4 to 0.95). No significant differences in toxicity grade 3/4 were found between groups, except for hypertriglyceridemia (10% v 0%) in RA/PC (P = .05). Immunohistochemistry and reverse-transcriptase polymerase chain reaction assays showed expression of RAR-β2 in normal tissues of all tumor samples, but only 10% of samples in the tumor tissue. Conclusion Adding ATRA to chemotherapy could increase RR and PFS in patients with advanced NSCLC with an acceptable toxicity profile. A phase III clinical trial is warranted to confirm these findings.
17
Wallace, J. A., G. Locker, S. Nattam, K. Kasza, K. Wade-Oliver, W. M. Stadler, E. E. Vokes, and H. L. Kindler. "Sorafenib (S) plus gemcitabine (G) for advanced pancreatic cancer (PC): A phase II trial of the University of Chicago Phase II Consortium." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4608. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4608.
Full textAbstract:
4608 Background: The ras oncogene is mutated in about 90% of PC, leading to constitutive activation of the Ras-Raf-MAPK signal transduction pathway. Sorafenib an inhibitor of B-raf, VEGFR2, and PDGFR-B, has in vitro activity against PC cell lines dependent on mutant Ras activation, and has anti-tumor activity in PC xenograft models. In a phase I trial of SG, 57% of PC patients (pts) had stable disease (SD) (Siu, 2003). Methods: We conducted a multi-center phase II trial of SG in advanced PC pts who had: no prior chemotherapy for metastatic disease, PS 0–1, measurable disease. Primary endpoint: response. The Simon 2-stage trial design required 1 response in 12 evaluable pts for 2nd stage. Pts received S 400 mg orally twice daily days (D) 1–28, and G 1000 mg/m2 over 30 minutes D 1, 8, 15 Q28D. CT scans: Q2 cycles. 17 pts enrolled at 4 sites 9/04–12/05. Pt characteristics: male 47%; median age 62 (range 50–85); PS 0 24% 1 76%; stage IV 94%; prior radiation 12%; liver metastases 81%. Results: 17 pts evaluable for toxicity, 13 for response. 61 cycles of SG have been given (median 2, range 1–12). There were no objective responses; 3 pts (23%) had SD. 1 pt with SD remains on treatment after 12 cycles. Median overall survival: 4.0 months (95% CI: 3.4, 5.9). Median progression-free survival: 3.2 months (95% CI: 1.6, 3.6). Grade 3/4 hematologic toxicities (% pts): neutropenia 29%; thrombocytopenia 6%; neutropenic fever 0%. Grade 3 non- hematologic toxicities: thrombosis 18%; fatigue 18%; rash 12%; dehydration 12%; nausea 12%; hand-foot syndrome 12%; hypertension 6%; diarrhea 6%; GI bleeding 6%. Conclusion: The study did not meet response criteria to proceed to a second stage of accrual. SG is inactive, though well-tolerated, in advanced PC pts. Supported by NCI grant N01-CM-62201. [Table: see text]
18
Hu, Xing-Sheng, Yuan-Kai Shi, Lin Wang, Lin Lin, Xiao-Hong Han, Zhi-Yun Meng, Gui-Fang Dou, and Yan Sun. "Phase Ib study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e19075-e19075. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e19075.
Full textAbstract:
e19075 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Synergistic effect of chidamide combined with paclitaxel and carboplatin (PC) have been demonstrated in various in vitro studies. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas.This phase Ib study was designed to assess the safety and pharmacokinetics of chidamide plus PC in pts with advanced non-small cell lung cancer (NSCLC). Methods: Chemonaive pts with stage IIIb or IV NSCLC were treated with the escalating doses of chidamide (20, 25, and 30mg) plus PC. Chidamide was oral administered twice per week. Paclitaxel (175 mg/m2) and carboplatin (AUC 5 mg·min/mL) were given both on day 1 every 3 weeks. Pts with response or stable disease after four cycles maintained single chidamide therapy until disease progression or unacceptable toxicity. Results: No DLT was observed in the 20 mg (n=3) and 25 mg (n=3) cohorts. 2 DLTs occurred in the 30 mg cohort (n=4), where 1 pt experienced grade 4 thrombocytopenia at the end of the first cycle, and the other developed grade 3 neutropenia and grade 2 thrombocytopenia resulting in the delay of the 2nd treatment cycle for > 14 days. Therefore, chidamide in 25 mg was determined to be the MTD with this combination regimen. ≥ Grade 3 toxicities were thrombocytopenia (n=3) and neutropenia (n=1). 1 pt experienced grade 1 prolonged QTc. Co-administration had no significant effect on clearance of either chidamide or paclitaxel. 1 pt in the 20 mg cohort had confirmed partial response. Of 5 pts with brain metastases, 2 of them had complete disappearance of brain tumors after 4-cycle treatment. Conclusions: Chidamide plus PC was safe and well tolerated, with no apparent chidamide-paclitaxel pharmacokinetic interaction. Preliminary efficacy results suggest that chidamide combined with PC could provide benefit to NSCLC pts, with a potential interest of further observation of brain metastasis control in NSCLC with this regimen. Clinical trial information: ChiCTR-ONC-12002283.
19
Fajardo Hermosillo, L. D. "AB0286 EFFICACY OF MYCOPHENOLATE MOFETIL PLUS RITUXIMAB COMPARED WITH INTRAVENOUS CYCLOPHOSPHAMIDE PLUS RITUXIMAB IN PATIENTS WITH RELAPSING LUPUS NEPHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1169.1–1169. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1612.
Full textAbstract:
Background:Lupus nephritis (LN) remaining as one of the most devastating manifestations of systemic lupus erythematosus (SLE). Only 60% of patients with LN achieve a complete (CR) or partial remission (PR) with mycophenolate mofetil (MMF) or intravenous (iv) cyclophosphamide (CY) plus corticosteroids. Of those nearly one-half will have a relapse following maintenance therapy [1]. Rituximab (RTX) is considered a treatment of relapsing LN [2]. Although potential benefits have been revealed in descriptive studies, efficacy has not been established in randomized trials [3,4].Objectives:This study compares the efficacy achieving a CR or PR with MMF+RTX versus iv CY+RTX in patients with relapsing LN.Methods:Mexican SLE patients classified by SLICC 2012 criteria were recruited from 2013 to 2019 with LN diagnosed by renal biopsy who previously having achieved a CR with MMF or iv CY followed by the maintenance therapy with azathioprine (AZA) or MMF and subsequently present relapsing LN consisting of a new active urinary sediment (US), worsening proteinuria and renal function. Demographic, renal clinical and paraclinical variables were examined. All patients received oral prednisone (1 mg/kg/d) accompanying MMF 3 g/d or CY 0.5–1 g/m2 monthly plus RTX 1 g at 0 and 14 days. The data were evaluated at 0, 6, 12 and 24 month(s) after the start both treatments. CR was defined as normal serum creatinine (SCr), inactive US, plus 24-Hour Urine Protein (24hUP) <500 mg/d and PC was established as 50 percent improvement in renal parameters. Fisher’s exact and Student´s-t tests were performed by univariate analysis.Results:Of nine SLE patients with relapsing LN, seven were women. The mean age [standard deviation (SD)] was 25.1 (6.4) years. The mean time at the onset of SLE (SD) was 3.44 (1.12) years ago. Four and five patients had class IV and IV/V LN respectively. Time of relapsing LN after of CR (SD) was 21.2 (7.17) months. Seven patients used CY followed by AZA and two employed MMF previously of relapsing LN. The mean of basal SLEDAI and SLICC (SD) were 19.11(3.2) and 1.22 (0.44) respectively. The mean of basal 24hUP (SD) was 4.67 (2.6) g/d and sCr (SD) was 2.0 (0.84) mg/dl. Five patients used MMF+RTX and four patients utilized CY+RTX. No statistically significant differences were found for CR, PR, 24hUP, sCr, US, anti-dsDNA and complement between both groups. At 6 months one patient achieved a CR and six reached a PR. At 12 months four patients fulfilled a CR and seven had a PR. Finally, at 24 months seven patients showed a CR and a CP. Only two patients did not achieve a CR or PR at 24 months.Conclusion:This study suggests that the most of SLE patients with relapsing LN treated with CY or MMF plus RTX achieved CR or PR at 24 months, although were no found differences between both treatments. However, these observations must be confirmed in larger and prospective studies.References:[1]Ann Rheum Dis 2020;79(6):713;[2]Nephrol Dial Transplant 2019;34(1):22;[3]Clin J Am Soc Nephrol 2009;4(3):579;[4]Arthritis Rheum 2012;64(4):1215Disclosure of Interests:None declared
20
Hassan, Raffit, Thierry Marie Jahan, Hedy Lee Kindler, Lyudmila Bazhenova, Martin Reck, Ira Pastan, Alison Ellis, et al. "Amatuximab, a chimeric monoclonal antibody to mesothelin, in combination with pemetrexed and cisplatin in patients with unresectable pleural mesothelioma: Results of a multicenter phase II clinical trial." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 7030. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7030.
Full textAbstract:
7030 Background: Amatuximab (MORAb-009) is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in many cancers including malignant mesothelioma (MM). Based on safety of amatuximab in phase I clinical trial and pre-clinical studies showing synergy in combination with chemotherapy, a single arm phase II study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in pts. with MM. Methods: Eligibility criteria included pts. with unresectable epithelial or biphasic pleural MM, no prior chemotherapy and KPS > 70%. Pts. received amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m2 and C 75 mg/m2 (PC) given on day 1, of each 21 day cycle for 6 cycles. Pts. with objective response or stable disease received amatuximab monotherapy until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), objective response rate and safety of amatuximab with PC. Results: From 2/2009 to 10/2010, 89 pts. were enrolled at 26 sites. Pt. characteristics: median age 67 yrs. (range 46-80), 78% male, 70% with KPS >90%, 89% epithelial MM, 11% biphasic MM and 88% had stage III/IV disease. Median number of PC plus amatuximab cycles was 5 (range 1-6) and 56 (63%) pts. received single agent amatuximab. In addition to the expected toxicity from PC, hypersensitivity reactions (12.4%; Grade 3/4=4.5%) from amatuximab were noted. By independent radiological review 30 (39%) pts. had partial response and 39 (51%) had stable disease. PFS at 6 months was 52% (95% CI: 39.5-63.5) with a median PFS of 6.1 months (95% CI: 5.4-6.5). As of 1/10/12 the median OS was 14.5 months (95% CI: 12.4-18.5) with 31 pts. still alive and 7 pts. receiving maintenance amatuximab. Conclusions: Amatuximab in combination with PC was generally well-tolerated in this study with 90% of pts. having an objective tumor response or stable disease by independent radiological review. Although PFS is not significantly different from historical results of PC alone, the median OS is 14.5 months with 35% of pts. still alive. Updated OS and biomarker data will be presented at the meeting.
21
Mellado, B., A. Font, L. A. Aparicio, E. Gallardo, J. R. Mel, A. Alcaraz, J. Areal, F. J. Gómez Veiga, N. Hannaoui, and P. Gascón. "Phase II trial of weekly docetaxel (D) and complete androgen blockade (CAB) prior to radical prostatectomy (RP) in high-risk localized prostate cancer (PC) patients (pts)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14515. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14515.
Full textAbstract:
14515 Background: Pts with high-risk localized PC have an increased risk of positive margins and recurrence after RP or radiotherapy alone. Neoadjuvant hormonotherapy (HT) has not shown a survival benefit prior to surgery, while outcomes are improved when HT is combined with radiotherapy. D-based chemotherapy improves survival in metastatic PC. These data support the investigation of multi-modality approaches to improve the aggressive behavior of high-risk localized PC. The main objective of this study was to assess the pathologic complete response (pCR) rate of the study combination. Secondary objectives were clinical activity, toxicity profile, time to progression and survival. Methods: Pts with clinical stage T1–2 (+ Gleason ≥ 7 (4+3) and/or PSA≥20 ng/mL) and T3 PC received 3 cycles of D (35 mg/m2 i.v. days 1, 8 and 15, every 28 days) concomitant with a depot goserelin (10.8 mg sc) plus flutamide (750 mg po daily for 3 months). RP was performed 2–4 weeks after the end of neoadjuvant therapy. Results: Fifty six pts have been included into the trial. Available data from 32 pts receiving neoadjuvant therapy were analyzed for this presentation. Median age was 69 years (53–75). Median follow-up was 3.6 months. Clinical stage was T1 (20%), T2 (53%) and T3 (27%); Gleason was ≥ 7 (4+3) in 25 (78%) pts. Eight (28%) pts had a PSA ≥ 20 ng/ml. A total of 85 cycles were administered (median 3) with a 100% median relative dose intensity for D. Grade III/IV toxicities per patient were liver toxicity (15.6%) and diarrhea (9.4%). Among the 16 pts who underwent RP to date, one (6%) achieved pCR, 11 (69%) had negative surgical margins and 9 (56%) had organ-confined disease. Conclusions: Neoadjuvant weekly D plus 3-month CAB is well tolerated and induces pCR in high-risk localized PC pts. Updated results will be available for the meeting. These results are encouraging while the true impact of neoadjuvant chemo-HT in this group of pts has to be determined in randomized trials. No significant financial relationships to disclose.
22
Whittaker, Naomi, Kristin Hueftle, Mary Warlaumont, Lauren Brin, David C. Olson, Apar Kishor Ganti, Xiang Fang, and Peter T. Silberstein. "A comparison of chemotherapy use in stage IV pancreatic cancer." Journal of Clinical Oncology 30, no. 34_suppl (December 1, 2012): 257. http://dx.doi.org/10.1200/jco.2012.30.34_suppl.257.
Full textAbstract:
257 Background: Palliative chemotherapy is the standard of care for stage IV pancreatic cancer patients (SFPC). Methods: This study compares the amount of chemotherapy given for SFPC across insurance types using the National Cancer Database (NCDB), which contains 70% of U.S. cancer cases. Results: The NCDB reported 115,512 patients diagnosed with SFPC from 2000 to 2009. Overall, 38.3% of SFPC patients received chemotherapy. The VAH (28.3%) and Medicare (29.7%) provided significantly less chemotherapy to SFPC patients as compared to Managed Care (48.2%), Private Insurance (46.7%), Tricare/Military (42.8%), Medicaid (37.8%), Medicare Plus Supplement (35.5%), and Uninsured (34.4%). From 2000 to 2009, the rate of chemotherapy for SFPC increased for both VAH (22.9% to 34.3%) and non-VAH (31.1% to 44.1%). At time of diagnosis, the percent of patients less than 60 at the VAH was 32%, non-VAH was 25.5% and Medicare was 7%. From age 20 to 59, the rate of chemo was stable at approximately 49%, but each successive decade demonstrated a marked reduction in use of chemotherapy (from 44% for 60 to 69 years of age to 21% for 80 to 89 and 5% for >90). The VAH PC population diagnosed with PC included 71.1% whites (W), 21.1% blacks (B), 4.8% Hispanics (H), 0.8% Asian-Pacific Islander (API), and 0.6% Native American (NA). Among all insurance types, only Medicaid (25%* B, 14%* H, 6%* API) and Uninsured (20% B, 15%* H, 4%* API) had a greater percentage of minorities. Compared to the average of all patients treated for SFPC (38.3%), blacks (34.7%*) and Hispanics (35.7%*) received less chemotherapy and whites received more (39.1%*). Conclusions: This is the largest study to analyze the use of chemotherapy in stage IV pancreatic cancer. Patients treated within the VAH were less likely to receive chemotherapy compared to all other patients except those with Medicare, who tend to be older at time of diagnosis. As age increases above 59, chemotherapy treatment for SFPC decreases. VAH patients receive less chemotherapy than Medicaid and Uninsured patients, though Medicaid and Uninsured have a greater percentage of minorities, who tend to get less chemotherapy for SFPC.
23
Kindler, H. L., D. Niedzwiecki, D. Hollis, E. Oraefo, D. Schrag, H. Hurwitz, H. L. McLeod, M. F. Mulcahy, R. L. Schilsky, and R. M. Goldberg. "A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4508. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4508.
Full textAbstract:
4508 Background: In a phase II trial in 52 PC pts, GB yielded a 21% response rate and a median survival of 8.8 months (mo) (Kindler, JCO 2005). These data led CALGB to conduct a phase III trial of GB vs. GP in advanced PC pts. Methods: This randomized trial was double-blind, placebo-controlled. Eligible pts had no prior therapy for advanced disease, PS 0–2, no tumor invasion of adjacent organs, no increased bleeding risk. Primary endpoint: overall survival (OS). Stratification: PS (0/1 or 2), disease extent (locally advanced or metastatic), prior radiation (RT) (yes/no). Statistics: 90% power to detect a difference in median OS of 6 vs. 8.1 mo. Treatment: Pts received G 1,000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg or P D 1, 15 Q28D. CT scans: Q2 cycles. Results: 602 pts enrolled 6/30/04–4/14/06. Based on a protocol-specified interim analysis with 64% of information on OS, the CALGB Data Safety Monitoring Board released study data in 6/06 because a futility boundary was crossed. Pts on treatment were notified and unblinded. Pt characteristics (302GB/300GP): male 58%/51%; median age 63.8/65.0; PS 2 9%/9%; stage IV 85%/84%; prior RT 11%/11%. Median follow-up: 11.3/11.7 mo. As of 12/22/06, 436 pts (224/212) have died (93% of total expected deaths at planned final analysis). Median OS 5.7/6.0 mo (95% CI: 4.9, 6.5/5.0, 6.9). Median failure-free survival 4.8/4.3 mo (95% CI: 4.3, 5.7/3.8, 5.6). Response (includes unconfirmed responses): complete (CR) 1.9%/3.0%; partial (PR) 11.2%/8.3%, stable disease (SD) 40.7%/35.7%. Disease control rate (CR/PR/SD) 54%/47%. 525 pts (268/257) are currently evaluable for toxicity. Median cycles 3.5/3.1 (p=0.09). Total mg/m2 G received 9095/8334 (p=0.22). Grade ¾ toxicity (%pts GB/GP): neutropenia 33%/30%; anemia 5%/8%; thrombocytopenia 12%/12%; hypertension 8%/2%; perforation 0.4%/0%; GI bleed 3%/2%; CVA 2%/2%; proteinuria 4%/1%; venous thrombosis 9%/9%. Conclusion: The addition of B to G does not improve survival in advanced PC. [Table: see text]
24
Kraut, M. J. "Phase II study of gemcitabine and carboplatin plus bevacizumab for stage III/IV non-small cell lung cancer: Preliminary safety data." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 17091. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.17091.
Full textAbstract:
17091 Background: The current standard of care for stage III/IV non-small cell lung cancer (NSCLC) is platinum-based chemotherapy. Bevacizumab (BV) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody that improves survival when used in combination with chemotherapy. In a randomized, phase II study of patients (pts) with advanced NSCLC, the addition of bevacizumab 15 mg/kg to paclitaxel/carboplatin (PC) resulted in prolonged survival and progression-free survival compared with PC alone (Sandler AB et al, ASCO 2005). In the present study, we are using BV 15 mg/kg in combination with gemcitabine/carboplatin (GC) for the treatment of NSCLC. Preliminary safety findings are summarized. Methods: Eligible pts with stage IV NSCLC, PS 0–1, and adequate hematologic, renal and hepatic function, were enrolled; pts with squamous cell carcinoma, tumor in the central airways, baseline hemoptysis, or brain metastases were excluded. GC/BV treatment was given in q 3-weekly cycles for 6 cycles, with BV continued in stable and responding patients. G 1250 mg/m2 was given on days 1 and 8 and C AUC 5 was given on day 1. BV 15 mg/kg was given on day 1. After 7 pts were enrolled, the study was amended to reduce the dose of G to 1000 mg/m2 on days 1 and 8 due to unacceptable neutropenia. Primary endpoint of the study is time to progression. Results: To date, 9 pts have received treatment; we report here the hematologic toxicity of the first 8, and non-hematologic toxicity of the first 7. There are 6 men and 2 women, median age 61.5 years. There was one episode of grade 4 thrombocytopenia, and Grade 3 events have been reported a number of patients: leukopenia (5 pts); neutropenia (4 pts); thrombocytopenia (4 pts); infection (1 pt); hemoglobin toxicity (1 pt); fatigue (1 pt); diarrhea (1 pt); dyspnea (1 pt); and dehydration (1 pt). Adverse events possible related to BV include Grade 3 hypertension (1 pt) and Grade 1 epistaxis (2 pts). No thrombosis or proteinuria has been reported. There have been no fatal toxicities. Conclusions: To date, the addition of BV to GC in pts with NSCLC is generally well tolerated and no unexpected adverse events possibly related to BV were observed. Enrollment is ongoing. [Table: see text]
25
Konski, Andre A., Joshua E. Meyer, Philip Agop Philip, Anthony Frank Shields, Michael J. Hall, Minsig Choi, Gail Duncan, Beth Adaire, Erin McSpadden, and Steven J. Cohen. "A phase I study of hyperfractionated low-dose radiotherapy (RT) as a chemotherapy sensitizer in combination with gemcitabine (G) and erlobtinib (E) in advanced pancreatic cancer." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 268. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.268.
Full textAbstract:
268 Background: G can sensitize pancreatic cancer (PC) to radiotherapy (RT). However, this approach requires lower doses of G and thus delays aggressive systemic treatment, which may lead to distant failure. In preclinical models, hyperfractionated low-dose RT sensitizes PC cells to G and erlotinib. We thus initiated a Phase I trial combining hyperfractionated low-dose RT combined with full dose G and a tyrosine kinase inhibitor, E, in the treatment of patients with advanced PC. Methods: Patients (pts) with locally advanced or metastatic PC confined to the abdomen and an ECOG performance status (PS) of 0-1, who had received 0-1 prior regimens (without G or E) and no prior RT were enrolled to successive cohorts in a 3+3 design. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4 hours on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Dosing cohorts were as follows (G in mg per m2, E in mg, XRT/fraction in cGy): 1 (1,000, 100, 40), 2 (1,000, 100, 50), 3 (1,000, 100, 60), 4 (1,000, 150, 60). Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: A total of 27 pts, (median age 64 yrs and 15 male), were enrolled between 11/24/08 and 4/12/12. 17 patients had a PS of 1. The majority of patients were stage IV. Seven pts were enrolled in dose level 1, with 1 pt experiencing a DLT of grade 3 ileus, 3 pts enrolled each in dose levels 2-4 without DLT and 11 pts enrolled in the expanded portion of level 4. Best response by RECIST in 24 evaluable pts and was as follows: partial response 8, stable disease 15 and progressive disease 1. One pt initially found to be unresectable at surgery was subsequently resected with only minimal microscopic residual disease. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Conclusions: This phase I study combining low-dose hyperfractionated RT as a sensitizer to full dose G plus E was well tolerated with the majority of pts experiencing either a partial response or stable disease. This represents a novel strategy worthy of further investigation in pts with advanced PC. Clinical trial information: NCT00761345.
26
Yoshitomi, Hideyuki, Hiroaki Shimizu, Hiroyuki Yoshidome, Masayuki Ohtsuka, Atsushi Kato, Katsunori Furukawa, Tsukasa Takayashiki, et al. "A randomized phase II trial of adjuvant chemotherapy with S-1 versus S-1 and gemcitabine (GS) versus gemcitabine alone (GEM) in patients with resected pancreatic cancer (CAP-002 study)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4056. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4056.
Full textAbstract:
4056 Background: Although the adjuvant therapy using GEM is now the standard therapy for patients with resected pancreatic cancer (PC), the prognosis still remains poor. Resent study demonstrated the non-inferiority of S-1 and superiority of GS to GEM with respect to progression free survival in patients with unresectable pancreatic cancer. Methods: Patients with invasive ductal PC who underwent radical surgery were enrolled. After stratification for R0/1, stage and institution, patients were randomized to receive GEM (GEM 1g/ m2, iv, d1, 8, and 15, q4w X12), S-1 (80/100/120mg/day based on BSA, po, d1-14, q3w X 16) or GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2, iv, d8, 15, q3w X 16) within 8weeks after operation. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 2y disease free survival (DFS) rate and secondary endpoints included overall survival (OS), and safety. Results: Between January 2007 and October 2010, 96 patients were randomized into the three arms of the trial (32 pts to each group). Patients’ characteristics were well balanced (GEM/S-1/GS) with regard to age (66/67/66y), tumor location (head 66/69/75%), tumor status (T3+4 88/78/91%), and nodal status (positive 75/69/75%). Until November 2012, 74 events (77%) have occurred for DFS. Two year DFS rate was 24.2%, 28.1% and 34.4% in GEM, S-1 and GS, respectively and there was no significant difference between groups. The median OS was 21m in GEM, 26m in S-1 and 27.9m in GS (Log rank test: N.S.). Grade 3/4 toxicities in GEM/S-1/GS were hematological 63/10/74% and non-hematological 17/10/23%, respectively. No treatment related death was observed during the study. Conclusions: S-1 and GS provided similar efficacy to GEM as the adjuvant chemotherapy for resected PC. According to the results, S-1 and GS is the adequate combination for phase III trial to examine the efficacy of adjuvant chemotherapy for PC. Clinical trial information: UMIN000002000.
27
Kindler, H. L., K. A. Bylow, H. S. Hochster, G. Friberg, K. Micetich, G. Locker, M. Kozloff, M. Moore, W. Sun, and E. E. Vokes. "A randomized phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 4040. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.4040.
Full textAbstract:
4040 Background: In a phase II trial of G + anti-VEGF antibody B in 52 PC pts, we reported a 21% response rate and median survival of 8.8 months (mo) (Kindler, JCO 2005). EGFR inhibitors C and E also have activity in PC. VEGF and EGFR pathways are interdependent; dual inhibition may be synergistic. Methods: We are conducting a multi-center, randomized phase II trial of GBC vs. GBE in advanced PC pts who have: no prior therapy for metastatic disease, PS 0–2, measurable disease, no tumor invasion of duodenum, no bleeding risk. Primary endpoint: response. Trial design: 2 parallel, Simon 2-stage designs; requires 6 responses in 27 evaluable pts for 2nd stage; 63 pts/arm. All pts receive G 1000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg D 1, 15 Q28D. Pts are randomized to C 400 mg/m2 D1, then 250 mg/m2 Q7D, or E 150 mg D1–5, 8–12, 15–26 Q28D. CT scans: Q2 cycles. 58 pts enrolled at 13 sites 9/04–12/05. Pt characteristics: male 66%; median age 61 (range 36–82); PS: 0/1/2: 52%/40%/8%; stage IV 95%; liver metastases 76%. Results: 49 pts (GBC/GBE 24/25) are evaluable for toxicity; 51 pts (27/24) for response. 232 cycles were administered (median 4, range 1–11). Grade ¾ toxicity (%pts GBC/GBE): neutropenia 29%/28%; anemia 4%/16%, thrombocytopenia 8%/24%, DVT-PE 17%/8%, CVA 4%/4%, GI bleed 4%/12%, hypertension 4%/4%, rash 13%/4%, pneumonitis 0%/8%, diarrhea 4%/4%; grade 5: bowel perforation 0%/4%, MI- CVA 0%/4%, other cardiac 4%/0%. Response: GBC 19% (1 complete, 4 partial), GBE 21% (5 partial). Stable disease 59%/67%. Median progression-free survival 3.6/3.6 mo (95%CI: 2.7, 4.7/2.7, 5.9), 6-month survival 41%/38% (95% CI: 11%, 71%/2%, 75%). Conclusion: GBC and GBE are active in advanced PC. Toxicity, principally related to B, is moderate. The trial proceeds to a 2nd stage if 1 more response is observed in each arm. Supported by NCI grant N01-CM-17102. [Table: see text]
28
Hoffe, Sarah E., Dae Won Kim, James Costello, Mokenge Peter Malafa, Todd Anthony Aguilera, Muhammad Shaalan Beg, Parag Parikh, et al. "GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with GC4711 in the treatment of unresectable or borderline resectable nonmetastatic pancreatic cancer (PC)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS4175. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps4175.
Full textAbstract:
TPS4175 Background: While systemic treatment of PC has improved, rates of surgical resection - considered optimum treatment - remain low. Patients with un-resectable or borderline PC still have poor outcomes, with both toxicity and disease progression during induction chemotherapy limiting the number eligible for surgery. SBRT practice to enhance margin negative resection or to provide local control, if inoperable after neoadjuvant therapy, has shifted to higher dose delivery (Mellon 2015, Colbert 2018), but timing and appropriate patient selection are under constant debate. SBRT delivery over 50Gy exhibits superior cell killing compared to conventionally fractionated RT but carries potential GI toxicity risk (Zhong 2017). GC4711 is a selective superoxide dismutase mimetic that converts superoxide to hydrogen peroxide. As radiation response modifiers, dismutase mimetics have the potential to increase tumor control without compromising radiation safety (Sishc, AACR 2019). GC4711 consistently augmented tumor control by SBRT in PC experimental xenograft mouse models. In a pilot phase 1/2 trial (GC4419-101), subjects with locally advanced PC were randomized to receive SBRT plus either the selective dismutase mimetic GC4419 or placebo. This pilot trial has demonstrated acceptable safety with SBRT (5 × 10-11Gy), as well as apparent improvements in survival, surgical resection, locoregional control, and time to distant metastases. Altogether, these data support the hypothesis that GC4711 may improve tumor outcomes and the benefit-risk ratio of 5-fraction SBRT delivering 50Gy by improving efficacy without increasing GI-toxicity. Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine the effect on overall survival of adding GC4711 to SBRT following 4 months of chemotherapy in subjects with un-resectable or borderline non-metastatic PC. Approximately 160 subjects will be enrolled at over 20 sites to receive GC4711 100 mg or placebo IV given as IV infusion over 15 min, prior to each of 5 SBRT fractions of 10Gy). Subjects judged operable will be explored within 8 weeks after SBRT. All subjects will complete 2 additional months of adjuvant chemotherapy. Primary end point is overall survival and secondary endpoints address resection rates, local and distant disease progression, and safety, while exploratory studies include ctDNA, tumor exome/transcriptome sequencing, and immune profiling, patient-reported symptoms (PRO-CTCAE), CA19.9 normalization, and radiomics. Colbert L, Rebueno N, Moningi S et al Advances in Radiation Oncology (2018) 3, 693-700 Mellon EA, Hoffe SE, Springett GM, et al Acta Oncologica, 2015;54:7 Zhong J, Patel K, Switchenko J, et al. Cancer. 2017 Sep 15;123(18):3486-3493. Sishc BJ, Saha D, Story MD. AACR PADC 2019 C52. Clinical trial information: NCT04698915.
29
Raju, R. N., M. Socinski, T. Stinchcombe, L. S. Couch, D. M. Kocs, R. Jotte, Y. Wang, J. Bromund, M. Marciniak, and C. Obasaju. "A prospective evaluation of quality of life (QOL) in a phase II trial of pemetrexed (P) plus carboplatin (Cb) ± enzastaurin (E) versus docetaxel (D) plus Cb as first-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e19050-e19050. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e19050.
Full textAbstract:
e19050 Background: E is a selective, oral serine/threonine kinase inhibitor. PCb has shown promising clinical activity in two phase 2 trials of advanced NSCLC. This open-label, three-arm trial was designed to assess PCb ± E versus a control arm of DCb. QOL may be an important consideration with the introduction of targeted agents such as E that have a different toxicity profile than traditional chemotherapeutic agents. Methods: Pts with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, and no prior systemic therapy were enrolled. Pts were equally randomized to one of three arms: (A) P 500 mg/m2 and Cb AUC 6 every 3 wks X 6 cycles with E given orally as a loading dose of 1200 mg or 1125 mg followed by 500 mg daily until disease progression; (B) The same regimen of PCb without E; or (C) D 75 mg/m2 and Cb AUC 6 every 3 wks X 6 cycles. Pts receiving P were also administered folic acid, vitamin B12 and steroid prophylaxis. Pts on D also received steroid prophylaxis. The Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire and FACT-Taxane toxicity subscale were used to evaluate QOL at baseline and every 3 weeks up to 18 weeks during treatment. A best overall response of improved or worsened was defined as an increase or decrease from baseline to last patient visit of ≥ 0.5 standard deviations of baseline scores. Results: The intent-to-treat population of this study consisted of 218 randomized pts (PCE: 72, PC: 74, DC: 72). Baseline and ≥ 1 post-baseline score was obtained from 54 pts receiving PCE (75%), 62 pts receiving PC (84%), and 54 pts receiving DC (75%). QOL data are summarized in the table below. Conclusions: Across treatment groups, differences in mean scores were not statistically significant. In addition, differences in classification of improved, stable, or worsened were not statistically significant across treatment groups. [Table: see text] [Table: see text]
30
Strumberg, Dirk, Beate Schultheis, Matthias Philip Ebert, A. Kerkhoff, Ralf Dieter Hofheinz, Dirk M. Behringer, Wolfgang E. Schmidt, et al. "Phase II, randomized, double-blind placebo-controlled trial of nimotuzumab plus gemcitabine compared with gemcitabine alone in patients (pts) with advanced pancreatic cancer (PC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4009. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4009.
Full textAbstract:
4009 Background: FOLFIRINOX significantly increases survival in metastatic PC compared to gemcitabine, but its use is limited to selected pts, due its high toxicity. In the majority of cases, gemcitabine (gem) remains the mainstay of palliative treatment, although its modest impact on survival and disease progression. The addition of the EGFR tyrosine kinase inhibitor erlotinib prolonged median survival for only 2 weeks.This study was aimed to investigate the effect of adding Nimotuzumab (nimo), an anti-EGFR monoclonal antibody, to first-line gemcitabine, in PC. Methods: Pts with previously untreated, unresectable, locally-advanced or metastatic PC were randomly assigned to receive gem: 1000 mg/m2/ 30-min iv once weekly (d1, 8, 15; q28) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or placebo, until progression or unacceptable toxicity. Primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Secondary endpoints included PFS, safety, objective response rate (ORR), QoL. Results: Between 9/2007- 10/2011 a total of 192 pts were randomized (average age 63.6 ±10 years; 60% male; 69% ECOG PS 0), and 186 were evaluable at the ITT analysis. One-year OS was 19.5 % with gem+placebo and 34.4% with gem+nimo (HR=0.69; p=0.034). Median OS and PFS were 6.0 mo in the gem+placebo group, vs. 8.7 mo in gem+nimo (HR=0.83; p=0.21), and 3.7 vs. 5.4 mo, respectively (HR=0.73; p=0.06). One-year PFS was 9.5 % for gem+placebo, compared with 21.5% for gem+nimo (HR=0.71; p=0.05). Significantly, in pts ≥ 62 years (60% of the population), median OS and PFS were 5.2 mo in the gem+placebo group vs. 8.8 mo in gem+nimo (HR=0.66; p=0.034), and 3.2 in gem+placebo vs. 5.5 mo in gem+nimo group, respectively (HR=0.55; p=0.0096). Nimo was safe and well tolerated, and no grade 3/4 toxicities were observed. Thirteen % of pts experienced grade 1/2 skin toxicity. Conclusions: This randomized study clearly showed that nimo in combination with gem is safe and well tolerated. The 1-year survival rate is significantly improved. Especially pts ≥ 62 years seem to benefit, possibly due to a more aggressive biology in younger pts. Clinical trial information: NCT00561990.
31
Shipley, William U., Stephanie L. Pugh, Himu R. Lukka, Pierre Major, Niall M. Heney, David A. Grignon, Oliver Sartor, et al. "NRG Oncology/RTOG 9601, a phase III trial in prostate cancer patients: Anti-androgen therapy (AAT) with bicalutamide during and after salvage radiation therapy (RT) following radical prostatectomy (RP) and an elevated PSA." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 3. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.3.
Full textAbstract:
3 Background: Previous reports suggested that AAT when combined with salvage RT following RP in patients may improve prostate cancer control outcomes. Methods: Post-RP patients with pT3pN0 or with pT2pN0 and positive margins who had or developed elevated PSA levels from 0.2 to 4.0 ng/ml were randomized on a phase III, double-blind, trial of RT + placebo (64.8 Gy in 36 fractions of 1.8 Gy) vs. RT + AAT (24 months bicalutamide, 150 mg daily) during and after RT. The primary end-point was overall survival. Trial design required 725 patients and provided 80% power to detect a reduction in death rate by at least 28.5% and a 1-sided significance level of 0.046. Results: From 3/98 to 3/03, 761 eligible patients (median age 65) were randomized to RT + AAT (384) or RT + placebo (377). 248 patients (33%) were pT2pN0 and 513 (67%) were pT3pN0. 671 (88%) had a PSA nadir after RP of < 0.5 ng/ml. 649 (85%) had an entry PSA value of <1.6, 112 patients (15%) had an entry PSA of 1.6-4. Median follow up was 12.6 years. Actuarial overall survival at 10 years was 82% for RT plus AAT and 78% for RT + placebo and a hazard ratio of 0.75 (95% CI: 0.58-0.98) with a 1-sided p value of 0.018 (2-sided p = 0.036). The 12-year incidence of PC central-reviewed deaths were 2.3% for RT + AAT and 7.5% for RT + placebo ( p< 0.001).The cumulative incidence of metastatic PC at 12 years was less in the RT + AAT arm, 14% (51 patients), vs. 23% (83 patients) in the RT + placebo arm (p < 0.001). Subgroup analyses of the relative benefits of the addition of AAT to RT are planned and will be presented. Late grade III and IV toxicity were similar in the AAT and placebo arms. The combined grade III and IV toxicities for RT + AAT and RT + placebo were: bladder 7.0% vs. 6.7%, bowel 2.7% vs. 1.6%. Gynecomastia differed significantly by treatment arm, 70% vs. 11%. Conclusions: 24 months of AAT using 150mg bicalutamide daily during and after salvage RT significantly improved long term overall survival and reduced the incidence of metastatic PC and PC death. Support: NCI grants U10CA21661, U10CA180868, U10CA180822, and U10CA37422 and AstraZeneca. Clinical trial information: NCT00002874.
32
Fukutomi, Akira, Takuji Okusaka, Kazuya Sugimori, Hideki Ueno, Tatsuya Ioka, Shinichi Ohkawa, Narikazu Boku, et al. "Updated results of the GEST study: Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer in Japan and Taiwan." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 4035. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.4035.
Full textAbstract:
4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p<0.001 for non-inferiority), which is consistent with prior results (HR=0.96, 97.5% CI: 0.78-1.18, p<0.001). In the GS group, median OS was 9.9 months (95% CI: 9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p=0.28 for superiority versus the GEM group). On subgroup analysis, GS was associated with a non-statistically significant trend toward better OS compared with GEM among patients with locally advanced disease and those with a PS of 1. Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and 15.9 months (95% CI: 13.0-19.7) in the GS group (HR=0.72, 95% CI: 0.51-1.03) among patients with locally advanced disease, and 6.2 months (95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9) in the GS group (HR=0.62, 95% CI: 0.46-0.83) among patients with a PS of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one of the standard treatments for advanced PC. As for GS therapy, there is room for further investigation.
33
Olowokure, Olugbenga Olanrele, Ivan Dario Bedoya, Michelle Lynn Mierzwa, Maria Patricia Torregroza, Alok kumar Dwivedi, Jiang Wang, Milton T. Smith, et al. "Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14714-e14714. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14714.
Full textAbstract:
e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m2 and nab-P=100mg/m2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline <1 (R<1-12,861), CA19-9 decrease > 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.
34
Greally, Megan, Vivian E. Strong, Sam S. Yoon, Joanne F. Chou, Marinela Capanu, David Paul Kelsen, Yelena Yuriy Janjigian, David H. Ilson, and Geoffrey Yuyat Ku. "Systemic chemo (CTX) plus surgery and intraperitoneal (IP) CTX for patients (pts) with gastric cancer (GC) and peritoneal carcinomatosis (PC)." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 117. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.117.
Full textAbstract:
117 Background: The role of IP CTX in pts with GC and PC is unclear. The PHOENIX-GC phase III study (J Clin Oncol 2018;35:1922) did not show overall survival (OS) benefit for IP CTX plus systemic CTX while a retrospective French study suggested benefit for IP CTX and cytoreductive surgery (J Clin Oncol 36:8 [abstr]). Prolonged survival may be possible in pts with chemosensitive disease (dz). Methods: We reviewed GC pts diagnosed with PC (+ve cytology and/or gross dz) at diagnostic laparoscopy (DL). We identified pts treated with gastrectomy and IP floxuridine 1,000mg/ m2/leucovorin 240 mg/m2 ×3d q14d and pts who had CTX alone. Pts with visible dz on imaging were excluded. Progression-free survival (PFS) and OS were calculated from surgery date and estimated using Kaplan-Methods in surgery + IP CTX pts. Pt characteristics were compared using Fisher’s exact test and Wilcoxon Rank-Sum tests. Results: From 2000-2017, 18 pts had surgery + IP CTX (IP); 45 pts received CTX alone. Median age was 50 in IP pts and 65 in CTX only pts (p = 0.002); 94% of IP pts were ECOG PS 0/1 vs. 78% in CTX only pts (p = 0.16). 56% and 67% of pts had gross dz at DL in IP and CTX only pts respectively; remaining pts had +ve cytology only. IP pts received CTX (72% 5-FU/platinum based) for a median 3.3 months before repeat DL. 14/18 pts cleared dz; four pts with residual dz (1 +ve cytology only) had gross dz at baseline. Fourteen pts had R0 resection; 83% of tumors were ypT3-4N+. 4 pts had R1 resection; three had residual gross PC at DL. Pts received IP CTX for a median of 1 month post surgery. Median PFS and OS were 12.4 and 23 months respectively in surgery + IP CTX pts. While there was no difference in PFS in pts with -ve vs. persistently +ve cytology at repeat DL following CTX (15.5 vs. 4.7 months, p = 0.3), median OS was improved in pts who cleared cytology (29 vs. 8 months, p = 0.01). Median PFS and OS were 7 and 13.5 months respectively in CTX only pts. Conclusions: Surgery and IP CTX may have a role in highly select pts with GC and +ve cytology or small-volume gross dz. While survival was encouraging, no pt had OS > 5 years. Surgery and IP CTX may be considered in pts who have a -ve repeat DL after initial CTX. Survival in CTX only pts is comparable with stage IV pts enrolled on clinical trials.
35
Mizuno, Nobumasa, Kenji Yamao, Yoshito Komatsu, Masaki Munakata, Atsushi Ishiguro, Taketo Yamaguchi, Shinichi Ohkawa, et al. "Randomized phase II trial of S-1 versus S-1 plus irinotecan (IRIS) in patients with gemcitabine-refractory pancreatic cancer." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 263. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.263.
Full textAbstract:
263 Background: Gemcitabine (Gem) monotherapy or Gem-based combination therapy is a standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. S-1, an oral fluoropyrimidine derivative, is commonly used for the second-line treatment of PC in Japan. Shitara et al previously reported that IRIS regimen showed that 44% of response rate (RR), 4.9 mo of median progression free survival (PFS), and 11.3 mo of median overall survival (OS), respectively. Therefore a randomized phase II trial was conducted to evaluate the efficacy and safety of IRIS compared with S-1 alone in the second-line setting. Methods: The inclusion criteria were as follows: (1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; (2) confirmed PD after Gem treatment; (3) ECOG PS, 0-1; (4) measurable metastatic lesion based on RECIST criteria; (5) age ≥ 20 years; (6) total bilirubin < 2.0 mg/dL. Patients were randomized to receive either IRIS (CPT-11 100 mg/m2, iv, d1,15 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q4w; Arm A) or S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm B). The primary endpoint was to compare PFS in Arm A and Arm B. Results: Of a total of 137 pts enrolled between Nov 2008 and Mar 2011, 127 were eligible (60 randomized to Arm A and 67 to B). Median PFS in Arm A and B was 107 and 58 days, respectively (HR= 0.767; 95% CI, 0.527-1.114; p=0.1750). Median OS in Arm A and B was 208 and 176 days, respectively (HR=0.749; 95% CI, 0.512-1.093; p=0.1338). RR was 18.3% in Arm A (11/60; 95% CI, 9.5-30.4) and 6.0% in Arm B (4/67; 95% CI, 1.7-14.6)(p=0.0311). The incidences of grade 3/4 toxicities were as follows: neutropenia (15.6% and 4.3%), anorexia (23.4% and 17.3%), nausea (6.3% and 2.9%), and diarrhea (3.1% and 2.9%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions: Although IRIS showed no significant improvement in PFS or OS compared with S-1 alone in this study, it showed significant advantage in RR, and favorable HR in both of PFS and OS. IRIS might have potential power to treat second-line PC patients. Further study is warranted. Clinical trial information: JapicCTI-080657.
36
MacKenzie, Shawn, Herbert Zeh, Laurence E. McCahill, Timothy D. Sielaff, Nathan Bahary, Thomas Edward Gribbin, John E. Seng, et al. "A pilot phase II multicenter study of nab-paclitaxel (Nab-P) and gemcitabine (G) as preoperative therapy for potentially resectable pancreatic cancer (PC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4038. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4038.
Full textAbstract:
4038 Background: Nab-P plus G is a new option for advanced PC. This combination was evaluated as a preoperative regimen for potentially resectable PC. Methods: Patients (pts, n=25) with resectable PC (NCCN criteria) were treated with 3 cycles of Nab-P (125mg/m2) & G (1000mg/m2) on day 1, 8, and 15, followed by surgical resection. The chosen endpoint was Grade III/IV histological changes (Arch Surg.127:1335-39:1992) in > 30% of resected tumor specimens. Results: Accrual is complete with 25 pts (median age 65, 10 F:15 M), 14/25 completed 3 cycles of treatment. Early drug discontinuation or drug interruption prior to the completion of 3 cycles occurred in 11 pts due to azotemia, cholangitis, pneumonia, catheter infection and pt decision. One pt had a fatal (grade 5) non-neutropenic aspergillus pneumonia. There was one episode of neutropenic fever (4%), and 3 episodes of cholangitis (12%) due to biliary stent malfunction. Other adverse events (grade 3/4) include neutropenia 64%, anemia 20%, dehydration 12%, nausea 12% and thrombocytopenia 12%. Dose reductions due to AEs were required in 5 pts, (3-neutropenia, 2-rash). Surgical resection was successful in 20/25 pts: 12- Pancreaticoduodenectomy, 8- Distal Pancreatectomy, 19/20 pts underwent an R0 resection. Surgical resection was not done in 5/25 pts due to: pre-operatively identified metastatic disease (2), blood vessel involvement at surgery (1), pt declined (1) and a pre-operative death (1).Post-operative tumor staging identified a complete response (n=1); stage IA (n=1); stage IIA (n=6); and stage IIB (n=12). Radiological partial response (PR) was documented in 4 pts prior to surgery. CA19-9 levels decreased from baseline by > 50% in 60% (n=15) of pts and by > 90% in 16% (n=4). Post-operative > 90% histological tumor response (Grade 3/4) was seen in 6 of 20 (30%) resected specimens. Conclusions: Preoperative therapy with Nab-P plus G is feasible with evidence of activity by radiological (PR in 16%), CA19-9 (decrease > 50% in 60% of pts) and pathological down staging (Grade 3/4 in 30% in resected tumor specimens). A larger study is warranted. Supported by Abraxis/Celgene Pharmaceuticals and the TGen foundation. Clinical trial information: NCT01298011.
37
Greally, Megan, Yaelle Tuvy, Brittanie M. Millang, Eileen Mary O'Reilly, Rona Yaeger, Leonard B. Saltz, and Geoffrey Yuyat Ku. "Actionable alterations (AA) in gastrointestinal (GI) cancers: Rate of detection and receipt of matched therapies (MT)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15677-e15677. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15677.
Full textAbstract:
e15677 Background: Next generation sequencing (NGS) is widely used in pts with advanced cancer to personalize care. Current NCCN guidelines endorse Her2, PD-L1 and MSI testing in esophagogastric cancer (EGC), RAS, BRAF, Her2 and MSI testing in colorectal cancer (CRC) and germline, somatic and MSI testing in pancreas cancer (PC). The proportion of GI cancer pts who receive MT based on NGS is unclear. Methods: We identified pts with advanced EGC (2016-18), PC (2017) and CRC (2016) who underwent NGS with MSK-IMPACT. We assessed the proportion of pts with ≥1 AA as defined by OncoKB (at the time of analysis, levels 1/2a were accepted practice and levels 2b/3/4 were investigational; Chakravaty, JCO PO 2017), those who received MT on trial or off label and 3 and 6 months (mos) progression-free survival (PFS). Results: We identified 260 EGC, 357 PC and 438 CRC pts. After excluding pts who had ongoing benefit from standard therapy (tx), were treated elsewhere or had no active stage IV disease, potential level 2/3/4 AAs occurred in 37% (n = 97) of EGC pts, 32.5% (n = 116) of PC pts and 26.7% (n = 117) of CRC pts (Table). 10, 1 and 17 pts with EGC, PC and CRC respectively were MSI. 1 pt in each subtype had an NTRK fusion (OncoKB level 1). In EGC, 6 pts (6.2% of those with AAs) received MT: 2 pts with MET amplification (a) and 1 each with BRCA2 mutation (m), TSC2m, ERBB2m and EGFRa. The pts with METa treated with crizotinib achieved 3 but not 6 mos PFS. In PC, 11 pts (9.5%) got MT: 10 pts for BRCAm and 1 for NTRK3 fusion. 9 pts with BRCAm treated with PARP inhibitors (i) achieved ≥3 mos PFS and 5 pts reached ≥6 mos PFS. The pt treated with NTRKi progressed rapidly. In CRC, 5 pts with ERBB2a and 9 pts with BRAFm received MT (12%). 3 pts and 2 pts treated with anti-Her2 tx achieved ≥3 and ≥6 mos PFS respectively. Of 6 pts treated with BRAF/MEKi plus irinotecan or anti-EGFR tx, all achieved ≥3 mos PFS; 3 reached ≥6 mos PFS. 3 pts received novel BRAF and ERK1/2i; none reached 3 mos PFS. Conclusions: NGS frequently identified OncoKB level 2 AAs. Few pts received MT, and of those, some achieved ≥6 mos PFS. Pts with CRC and PC received MT which subsequently became standard NCCN recommendations; therefore, a more current analysis may show increased MT use. Still, MT for level 3 and 4 alterations were rare, suggesting expectations of NGS must be managed appropriately. [Table: see text]
38
Zinner, Ralph, Jennifer M. Johnson, Madalina Tuluc, Joseph M. Curry, Adam Luginbuhl, Christopher C. Fundakowski, Andrew Yampolsky, et al. "Neoadjuvant nivolumab (N) plus weekly carboplatin (C) and paclitaxel (P) in resectable locally advanced head and neck cancer." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 6583. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.6583.
Full textAbstract:
6583 Background: Despite multimodality standard therapy, patients (pts) with resectable locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) are at high risk for recurrence. Pts with pathologic complete response (pCR) or major pathologic response (MPR) to neoadjuvant chemotherapy have improved overall survival. PD-1 checkpoint inhibitors are approved in combination with platinum-based chemotherapy in the 1st-line treatment of recurrent/metastatic SCCHN. We hypothesize the addition of N to wkly carboplatin C and P will increase the pCR rate at the primary site compared to historical controls. Methods: This is an investigator-initiated trial for pts with newly diagnosed (AJCC 8th) stage III-IV HPV- (oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L) or stage II-III HPV+ OP SCCHN without distant metastasis who are surgical candidates. Neoadjuvant chemo starting d1 is C AUC 2 IV wkly x 6 plus P 100 mg/m2 IV wkly x 6 plus N 240 mg IV q 2 wks x 3 with surgery on wk 8. The primary endpoint is pCR at the primary site. To estimate pathologic response, the resected pathology specimens are cut >1 section/cm. Using the Aperio Digital scanning system, slides are imaged, and then annotated by at least 2 pathologists for viable tumor vs. treatment effect with areas automatically calculated to yield the percentage of viable tumor. Our primary endpoint will be reached if 11/37 planned pts have a pCR at the primary site. Results: From 11/17-12/19, 27 pts received the study regimen and had surgery (1/27 had an unknown primary; thus, inevaluable for the primary endpoint). Of 27 pts, median age was 59 (46-83), women 31%, HPV+ 15%, OC 73%, OP 19%, HP 7%, L 4%; stage III 33%, stage IVA 67%. Gd 3 toxicities were in 37% pts; 1 pt febrile neutropenia, 3pts anemia, 1pt diarrhea, 1pt cellulitis and 1pt rash. Four pts had gd 3-4 neutropenia. Dose reductions were in 2 pts, and 4 pts had 1 wkly dose dropped. All 27 pts went to surgery, none with PD by CT; all with negative margins. One pt died with rapid recurrence; no other recurrences (median f/u 13 mos). Our primary endpoint was met; 11/26 (42%) pts (excluding pt with unknown primary) had a pCR at the primary site. 9/23 (39%) HPV- pts, had a pCR. MPR or pCR was 18/26 (69%) and in HPV- pts, 15/23 (65%). 2/11 pts had microscopic residual disease in 1 LN each. Conclusions: The combination of N and wkly PC was well tolerated. The primary endpoint of pCR at the primary site in > 11/37 pts was met with the 27th pt. Accrual continues. Exploratory outcomes assessing markers of immune bias in tumor tissue and plasma are in process. Clinical trial information: NCT03342911 .
39
Bruhweiler, Fredrick C. "The Morphology and Physics of the Local Interstellar Medium." International Astronomical Union Colloquium 152 (1996): 261–68. http://dx.doi.org/10.1017/s0252921100036071.
Full textAbstract:
We are finally on the threshold of obtaining a coherent morphological and physical picture for the local interstellar medium (LISM), especially the region within 300 pc of the Sun. The EUVE is playing a special role in revealing this picture. This instrument can provide direct measurements of the the radiation field that photoionizes both hydrogen and helium. It also can yield direct measurements of the column densities of hydrogen, but especially He I and He II toward nearby white dwarfs. These observations suggest that the ionization in the Local Cloud, the cloud in which the Sun is embedded, is not in equilibrium, but in a recombination phase. Heuristic calculations imply that the the present ionization is due to the passage of shocks, at times greater than 3 × 106 years ago. The origin of these shocks are probably linked to the supernova which was responsible for the expanding nebular complex of clouds know as the Loop I supernova remnant, of which the Local Cloud is a part, extreme- UV radiation field, that which ionizes both hydrogen and helium in the LISM. Of the ISM within 300 pc, the volume appears to be predominantly filled by hot (106 K) coronal gas. This gas is laced with six largescale shell structures with diameters ~100−150 pc including the long-recognized radio loops, Loop I−IV, as well as the Orion-Eridanus and Gum Nebulae are identified. An idea that has evolved in the literature for over two decades is that the kinematically-linked OB associations representing Gould’s Belt, plus the gas and dust of Lindblad’s Ring, require that previous supernova activity and stellar winds carved out a 400–600 pc diameter cavity some 3 to 6 × 107 yr ago. This activity produced a pre-existing low density region, into which the present young loop structures have expanded. The outer boundaries of the identified expanding loop structures, inside this preexisting cavity, delineate the periphery of the the mis-named “local interstellar bubble.” Thus, this picture naturally explains some of the problems often associated with the presence of this low density region exterior to Loop I.
40
Ko, Andrew H., Patrick B. Murphy, James D. Peyton, Dianna Shipley, Ahmed Al-Hazzouri, Frank A. Rodriguez, Mark S. Womack, et al. "RAINIER: A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (nab-P) combined with apatorsen (A) or placebo (Pl) in patients (pts) with metastatic pancreatic cancer (mPC)." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 419. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.419.
Full textAbstract:
419 Background: Heat shock protein 27 (Hsp27) is over-expressed in PC, enabling tumor growth and metastasis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m2 IV, nab-P 125mg/m2 IV days 1, 8, and 15. Restaging was every 2 cycles. Serum Hsp27 levels were collected at baseline and on treatment. Primary endpoint compared overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Demographics were similar for both arms. 36% of pts on Arm A and 48% of pts Arm B discontinued due to progressive disease, and 24% and 14% due to adverse events (AEs). There was a higher incidence of ≥Grade (G) 4 and serious adverse events (SAEs) in Arm A. The most frequently reported G 3/4 treatment-related AEs were anemia (20%), neutropenia (17%), and fatigue (16%) on Arm A and anemia (27%), neutropenia (19%), and thrombocytopenia (13%) on Arm B. Overall RR was 18% on each arm. With a median f/u of 9.1 mos, median PFS and OS are 2.7 and 5.2 mos on Arm A and 3.8 and 6.9 mos on Arm B (p=NS). Correlative analyses between Hsp27 expression and clinical outcomes will be presented. In a statistical model using only Arm B data, 3 base attributes, ECOG >0, liver mets, and neutrophil levels had a strong prognostic relationship to OS. Conclusions: This study showed no improvement in clinical outcomes adding A to gem plus nab-p. G 4 AEs and SAEs were increased with A. We await analysis for Hsp 27 and CA 19-9 levels and further analysis to identify any pt subgroup who might have benefited from the experimental treatment. Clinical trial information: NCT01844817.
41
Edelman, M. J., C. P. Belani, M. A. Socinski, R. Ansari, C. K. Obasaju, M. J. Monberg, R. Chen, and J. Treat. "Incidence and outcomes associated with brain metastases (BM) in a three-arm phase III trial of gemcitabine in combination with carboplatin (GC) or paclitaxel (GP) versus paclitaxel plus carboplatin (PC) for advanced non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8076. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8076.
Full textAbstract:
8076 Background: A limited number of randomized phase III studies of advanced or metastatic NSCLC have included a mixed population of patients (pts) with and without BM at presentation. Analyses of pts with lung cancer from the 1970s and 1980s indicated that the incidence of BM at the time of diagnosis was approximately 10%. Methods: 1135 chemonaïve pts with stage IIIB or IV NSCLC were randomized to receive: G 1000 mg/m2 d 1, 8 plus C AUC 5.5 d 1; or G 1000 mg/m2 days 1 and 8 plus P 200 mg/m2 d 1; or P 225 mg/m2 plus C AUC 6.0 d 1. Stratification was based on stage, baseline weight loss, and presence or absence of BM. Cycles were repeated every 21 d up to 6 cycles or disease progression. Pts who developed BM as the only evidence of progression were able to be treated with whole brain radiation and steroids and remained on study. Results were retrospectively analyzed in by presence or absence of BM at study entry. Results: BM rates by subgroup were as follows (%): overall (17.1), nonsquamous (19.3), squamous (6.9), <70 y (21.3), ≥ 70 y (7.1), female (19.2), male (15.7), Caucasian (16.7), African American (18.8%), Hispanic (22.2), PS 0 (12.9), PS 1 (19.7), weight loss <5% (18.3), weight loss ≥ 5% (15.1), and stage IV (19.0). Among pts with (N=194) and without (N=941) BM, response rates=28.9% and 29.1%, median survival = 7.7 mos (95% CI: 6.7, 9.3) and 8.6 mos (95% CI: 7.9, 9.5), and median time to progression = 4.3 mos (95% CI: 3.4, 5.6) and 4.6 mos (95% CI: 4.2, 5.1), respectively. Rates of grade 3 or 4 adverse events were not different among pts with and without BM. Median survival among pts with BM was 7.6 mos for GC (N=66, 95% CI: 6.3, 10.1), 8.2 mos for GP (N=64, 95% CI: 4.6, 10.5), and 7.7 mos for PC (N=64, 95% CI: 6.1, 10.2). Conclusions: 1) The higher incidence of BM (17.1%) observed in this trial may be related to the increasing incidence of adenocarcinoma, or to the increasing sensitivity of imaging modalities. 2) There was no difference in response, time to progression or survival for pts with or w/o BM. [Table: see text]
42
Ansari, R. H., M. J. Edelman, C. P. Belani, M. A. Socinski, C. K. Obasaju, M. J. Monberg, R. Chen, and J. Treat. "Outcomes for the elderly (≥70 years) from a three-arm phase III trial of gemcitabine in combination with carboplatin (GC) or paclitaxel (GP) versus paclitaxel plus carboplatin (PC) for advanced non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8052. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8052.
Full textAbstract:
8052 Background: Approximately 50% of lung cancer patients (pts) are ≥ 70 y, however, this population has been historically underrepresented in clinical trials. Even among pts ≥ 70 y, doublet chemotherapy has been shown to be superior to single-agent therapy (Lilenbaum JCO 2005, Sederholm JCO, 2005), and the efficacy and safety of platinum-based chemotherapy doublets in NSCLC pts ≥ 70 years with good PS have been reported to be similar to those in younger pts (Fossella, ASCO 2003, #2528, Kelly, ASCO 2001, A-1313). The current analysis examined whether any differences were present by age in a three arm trial of GC or GP versus a standard regimen of PC. Methods: 1135 chemonaïve pts with stage IIIB or IV NSCLC were randomized to receive: G 1000 mg/m2 d 1,8 plus C AUC 5.5 d 1; or G 1000 mg/m2 d 1,8 plus P 200 mg/m2 d 1; or P 225 mg/m2 plus C AUC 6.0 d 1. Stratification was based on stage, baseline weight loss, and brain metastases. Cycles were repeated every 21 days up to 6 cycles or disease progression. Clinical results were retrospectively analyzed in by patient age. Results: See Table . Conclusions: In this trial of commonly used regimens for advanced NSCLC, pts 70–74 years of age had significantly longer survival than pts 75–79 years of age. Pts 80+ years of age also had lower survival than the 70–74 year age group, but this difference was not statistically significant. No pts 80+ years of age had brain metastases at study entry. There was no clear pattern with respect to the effectiveness of individual treatment regimens by age group. [Table: see text] [Table: see text]
43
Basu, Gargi D., Kevin Drenner, Audrey Ozols, Candyce M. Bair, Tracey White, Janine R. LoBello, Thomas Royce, and Sunil Sharma. "Whole exome and transcriptome sequencing of colorectal and pancreatic cancer." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15666-e15666. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15666.
Full textAbstract:
e15666 Background: Integration of Whole Exome Sequencing (WES) into clinical cancer therapeutics has revolutionized medicine in recent years. DNA sequencing alone may miss clinically actionable variants or identify aberrations that are not being transcribed. In this study we investigated the utility of integrating DNA and RNA sequencing in clinical samples. Methods: A cohort of 32 patient samples were analyzed by WES and RNA sequencing. Differential expression analysis was performed using a cohort of controls. Pathway analysis was performed using Ingenuity Pathway Analysis. WES and RNA analysis detected alterations including SNVs, indels, copy number events, fusions, alternate transcripts, TMB, MSI status and differential expression. Results: A total of 25 CRC (39-78yrs) and 7 pancreatic cancers (PCs) (51-91 yrs) were profiled by WES and RNA seq. A 66 yr old pt with neoplasm of rectosigmoid junction tumor was found to be KRAS wildtype and was treated with cetuximab plus FOLFIRI. Patient failed therapy after 2 yrs and sequencing revealed MET amplification which is a known mechanism of resistance to cetuximab treatment. Further, RNA expression analysis showed 44-fold increase in MET expression along with overexpression of AREG and EREG. Out of the 7 PCs, 3 cases that did not harbor KRAS mutation were found to harbor VTCN1/NRG1 fusion, FGFR1/G3BP2 fusion and BRAF V600E mutation respectively. A 50 year-old stage IV metastatic (met) PC pt was treated with standard of care regimens. Upon relapse the sample was found to harbor VTCN1/NRG1 fusion along with a TERT promoter mutation. RNA expression analysis revealed 54-fold increased expression of NRG1 which may lead to clinical trial enrollment. A 52 year-old male met Stage IV PC, was treated with rucaparib and irinotecan based on prior sequencing data. Upon relapse, the pt went on ATR inhibitor (BAY1895344) and progressed very quickly. Sequencing of the met lesion was found to harbor FGFR1/G3BP2 fusion which was also confirmed by RNA expression. A 55 year-old met pt with PC was treated with standard chemotherapy. Upon disease progression pt was sequenced and based on presence of BRAF V600E, pt was treated with trametinib and dabrafenib. Following disease progression on BRAF/MEKi, met sample was resequenced and RNA expression analysis found increased expression of MET, MACC1 and SMAD7 and 4-fold decrease in PTEN which could potentially cause resistance to BRAF/MEKi therapy. Conclusions: Our study highlights the utility of comprehensive testing integrating genomic and transcriptomic data, in identifying targeted therapy options for cancer patients.
44
Jeske, S. J., M. I. Milowsky, C. R. Smith, K. A. Smith, N. H. Bander, and D. M. Nanus. "Phase II trial of the anti-prostate specific membrane antigen (PSMA) monoclonal antibody (mAb) J591 plus low-dose interleukin-2 (IL-2) in patients (pts) with recurrent prostate cancer (PC)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 15558. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15558.
Full textAbstract:
15558 Background: The de-immunized mAb J591 recognizes the extracellular domain of PSMA and was engineered to induce antibody-dependent cellular cytotoxicity (ADCC). Low-dose IL-2 results in the clonal expansion of NK cells and may enhance ADCC. We conducted a phase 2 trial to determine the efficacy and toxicity of mAb J591 plus low-dose subcutaneous (SC) IL-2 in pts with recurrent PC. Methods: 17 pts with recurrent PC (2 groups: 11 with PSA relapse only; and 6 with progressive castrate metastatic disease) received continuous low-dose SC IL-2 (1.2 x 106 IU/m2/day) daily for 8 weeks with mAb J591 (25 mg/m2 IV) weekly on weeks 4, 5 and 6 (1 cycle). Pts could receive a maximum of 3 cycles. Results: 16 evaluable pts received up to 3 cycles of therapy (16 pts, one cycle, 9 two cycles and 2 three cycles). Toxicity was mild and limited to fatigue and injection site reactions. At the end of cycle 1, PSA was stable (-50%<change in PSA<25%) in 9 of 16 patients, with PSA declines up to 34%. No PSA decline >50% was observed. A post-hoc analysis of PSA kinetics showed 5 patients had a reduction in their PSA slope of =25%; 8 of the remaining 11 patients demonstrated PSA stabilization (- 25%<change in PSA slope<25%). PSA response was most commonly observed during weeks 4–6 of the cycle correlating with mAb administration. Flow cytometric analysis of peripheral blood mononuclear cells revealed an average increase in absolute NK cell count of 107% at week 4 and 117% at the end of cycle 1. Conclusions: The combination of mAb J591 with low-dose IL-2 was well tolerated and inhibited PSA kinetics in some patients, however no responses were seen. Repetitive dosed mAb J591 is a viable strategy for use in combination with immune modulatory or other therapies in recurrent prostate cancer. No significant financial relationships to disclose.
45
Goldstein, D., N. Spry, G. Van Hazel, C. Underhill, D. Kotasek, J. Harvey, M. Links, J. Shapiro, B. Iacopetta, and Eli Lilly Australia. "Combined modality therapy for pancreatic carcinoma: An Australian Pancreatic Cancer Group study of the addition of gemcitabine (G) to concurrent infusional 5-fluorouracil (CI 5FU) and 3D conformal radiotherapy (RT)—Final outcomes." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 4104. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.4104.
Full textAbstract:
4104 Background: This open-label Phase II study (B9E-AY-S168) examined whether CI 5FU plus 3D conformal planning RT is well tolerated and may be combined with G pre and post chemoradiotherapy in patients (pts) with pancreatic cancer (PC). Methods: Eligible pts were enrolled in two strata: (1) inoperable PC in head or body without metastases (LAD) or (2) resected PC at high risk of relapse (Surg). G was given at 1000 mg/m2 weekly for 3 wks followed by 1 wk rest and a 5–6 wk period of RT and concurrent CI 5FU (200 mg/m2/day). The defined target volume was treated to 54Gy in 30# of 1.8Gy (LAD) or 45Gy in 25# (Surg). After 4 wks rest, G was given for 12 wks. Results: 63 pts were enrolled: 39 females, 24 males; mean age 61 yr, range 31–79; 43% ECOG PS 0, 51% PS 1, 5% PS 2. Follow-up was 2 yr. 1- and 2-yr survival (KM) were 46% and 10% (LAD) and 59% and 27% (Surg). 1- and 2-yr local control (KM) were 48% and 21% (LAD) and 80% and 80% (Surg). The % planned dose delivered was (i) G pre RT: 87.6% (LAD)/94.6% (Surg); (ii) 5FU: 100.7%/96.4%; (iii) RT: 96.2%/99.5%; (iv) G post RT: 67.4%/65.3%. The baseline CA 19.9 level was significantly associated with a shorter TTPD (p=0.0002) and a shorter survival time (p=0.0071). Using Time Dependent Covariate analysis, CA 19.9 levels were strongly associated with TTPD and survival (both p < 0.0001); a person with a 10-fold higher level has a 1.95-fold higher risk of death over the next time period than their counterpart (95% CI: 1.53–2.49-fold). In 22 pts we found no statistically significant associations between outcome and mutations in K-RAS or TP53 or with microsatellite instability. Grade 3/4 hematological and non-hematological toxicity was reported by 29 (46%) and 42 pts (67%), respectively. There was one treatment-related death. Conclusions: This approach to treatment is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomized trial. [Table: see text] [Table: see text]
46
Agarwal, Neeraj, Arun Azad, Joan Carles, Simon Chowdhury, Bradley Alexander McGregor, Axel Stuart Merseburger, Stephane Oudard, et al. "A phase III, randomized, open-label, study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy (NHT) in patients (pts) with metastatic, castration-resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021): TPS190. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.tps190.
Full textAbstract:
TPS190 Background: Cabozantinib inhibits multiple tyrosine kinases, including MET, VEGFR, RET, and TAM kinases (Tyro3, AXL, MER), involved in tumor growth and angiogenesis, and whose mutations and expression are associated with prostate cancer aggressiveness and poor prognosis. Targeting these kinases with cabozantinib may promote an immune permissive tumor environment and may enhance response to immune checkpoint inhibitors. In the ongoing phase 1b COSMIC-021 study of pts with solid tumors, cabozantinib plus the PD-L1 inhibitor atezolizumab, showed preliminary meaningful clinical activity in soft tissue disease and a tolerable safety profile for 44 pts with mCRPC (Agarwal et al., ASCO 2020; abstract 5564). We present the study design of a phase 3 trial of cabozantinib plus atezolizumab versus second NHT in pts with mCRPC. Methods: This randomized, open-label, controlled phase 3 study (NCT04446117) evaluates the efficacy and safety of cabozantinib plus atezolizumab versus second NHT (abiraterone or enzalutamide) in pts with mCRPC who previously received one NHT to treat metastatic castration-sensitive PC (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC. Additional eligibility criteria include histologically or cytologically confirmed adenocarcinoma of the prostate, measurable visceral disease or measurable extrapelvic adenopathy per RECIST 1.1 by investigator, prostate specific antigen progression and/or soft-tissue disease progression, ECOG 0 or 1, and age ≥18 years. Key exclusion criteria include prior nonhormonal therapy for mCRPC and uncontrolled significant illness. Eligible pts (N = 580) are randomized 1:1 to receive cabozantinib (40 mg PO QD) + atezolizumab (1200 mg IV Q3W) vs abiraterone (1000 mg PO QD) + prednisone (5 mg PO BID) or enzalutamide (160 mg PO QD). Designated NHT will differ from previous NHT taken. Randomization is stratified by: liver metastasis (yes, no), prior docetaxel treatment for mCSPC (yes, no), and disease stage for which the first NHT was given (mCSPC, M0 CRPC, mCRPC). Treatment will continue until there is no longer clinical benefit as determined by the treating investigator, unacceptable toxicity, or consent withdrawal. The multiple primary endpoints are progression-free survival per RECIST 1.1 by blinded independent radiology committee (BIRC) and overall survival. Additional endpoints include objective response rate per RECIST 1.1 by BIRC, safety, correlation of biomarkers with outcomes, quality of life and pharmacokinetics. Patient enrollment is ongoing. Clinical trial information: NCT04446117.
47
Kang, Hyunseok, Adrian Daniel Schubert, Paul Ladenson, Douglas Wilmot Ball, Jon Chung, Alexa Betzig Schrock, Jeffrey S. Ross, Vincent A. Miller, Philip J. Stephens, and Siraj Mahamed Ali. "Comprehensive genomic profiling of parathyroid carcinoma." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 6088. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.6088.
Full textAbstract:
6088 Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy, which can cause life-threatening hypercalcemia. Initial surgery is often noncurative, and adjunctive radiotherapy and previous chemotherapies have not been shown to be effective. Previous studies identified recurring mutations in CDC73 and PRUNE2in a limited number of patients. We queried whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 13 consecutive cases of relapsed/metastatic PC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 672x for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Total of 13 specimens were identified from 7 male and 6 female patients. The mean age of the patients in this study was 54 years (range 38 to 76 years). All (100%) cases were Stage IV at the time of CGP. Tumor mutation burden was generally low - median mutation load per mega base was 1.8. There were 58 total GA (4.5 GA/sample) and 10 CRGA (0.8 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (31%) and CDC73 (31%). MEN1 mutations were identified in 23% of cases. Frequent alterations in genes controlling cell cycle progression at G1 including CDKN1B, CDKN2A, CDKN2B and CDKN2C were identified (30%). The most frequent CRGA involved PTEN (23%), NF1 (23%) and KDR (15%). No alterations in BRAF or RETwere identified. A patient with KDR mutation treated with cabozantinib experienced > 50% drop in PTH level and radiographic partial response in 3 months. Conclusions: CGP identified previously unreported TP53 mutations in PCs and potentially actionable genomic alterations including PTEN, NF1 and KDR. Clinical benefit and response observed in a patient treated with VEGFR targeted therapy suggest that patients with this rare tumor may be candidates for targeted therapies.
48
Bonomi, P. D., J. Mace, R. D. Mandanas, M. Min, Y. Zhang, E. Rowinsky, and H. Youssoufian. "Phase II randomized, open-label study of cetuximab (Cet) and bevacizumab (Bev) in combination with paclitaxel (P) and carboplatin (C) in patients with stageIII/IV non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8046. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8046.
Full textAbstract:
8046^ Background: Cet, a monoclonal antibody (mAb) that specifically targets epidermal growth factor receptor (EGFR) and Bev (anti-VEGF mAb) combined with chemotherapy has resulted in superior survival compared to chemotherapy alone in some stage IV NSCLC trials. Combining both mAb's with chemotherapy might increase survival in stage IV NSCLC pts. Methods: Chemotherapy naïve advanced NSCLC patients with ECOG status <1, adequate hematologic, hepatic, and renal function received Cet (400 mg/m2 on Day 1 as initial dose and weekly thereafter at 250 mg/m2) plus Bev (15 mg/kg on Day 8 of each 3-week cycle) for 6 cycles in combination with either 6 cycles (Arm A) or 3 cycles (Arm B) of P (200 m/kg) and C (AUC=6) on Day 1 of each 3-week cycle. Patients without progressive disease (PD) after 6 cycles continued Cet until PD or other withdrawal criteria were met. Comparison of progression-free survival (PFS) for arm A vs B is the primary objective. Results: Accrual is completed. Data are available for 85 pts: 47% women, median age 65 yrs, and 88% Caucasian. Median PFS for arm A was 6.0 vs 4.2 months for arm B, hazard ratio of 0.57 for arm A relative to arm B. Objective response was Arm A=31% and B=30%. Most frequent AEs ≥Grade 3 in pts were neutropenia [9 (10.6%), A=8, B=1], fatigue [8 (9.4%), A=4, B=4], dermatitis acneiform [6 (7.1%), A=3, B=3].13 pts withdrew due to AEs (A=4, B=9), 4 were related to Cet (2 per arm). Two pts discontinued due to death (A=2, B=0) unrelated to Cet. Conclusions: Adding both mAb's to PC resulted in acceptable toxicity. The trend for superior PFS with 6 courses of PC suggests that 3 courses of PC are not optimal. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .
49
Herrera, Alex F., Hongli Li, Sharon M. Castellino, Sarah C. Rutherford, Kelly Davison, Andrew G. Evans, Angela Punnett, et al. "SWOG S1826: A Phase III, Randomized Study of Nivolumab Plus AVD or Brentuximab Vedotin Plus AVD in Patients with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 23–24. http://dx.doi.org/10.1182/blood-2020-136422.
Full textAbstract:
Although most patients (pts) with newly diagnosed stage III or IV Hodgkin lymphoma (HL) will be cured with initial therapy (tx), about 20-25% of pts will have relapsed or refractory (R/R) HL. The standard initial tx for adults with advanced stage HL, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), is associated with pulmonary toxicity due to bleomycin. Recent studies have demonstrated that in pts with a negative interim PET scan, the omission of bleomycin after 2 cycles is non-inferior with regards to survival. However, a significant proportion of pts have a positive interim PET scan and require escalation to BEACOPP - an effective but toxic regimen associated with secondary malignancies and infertility. Recently, the addition of brentuximab vedotin (BV) to AVD chemotherapy (BV-AVD) demonstrated improved modified and traditionally-defined progression-free survival (PFS) compared to ABVD. However, the BV-AVD regimen was associated with higher rates of neutropenia, sepsis, and peripheral neuropathy compared to ABVD, and there still was a ~20% failure rate. In adolescent and young adult pts with advanced stage HL, there is a similar ~20% failure rate using ABVE-PC (AB, vincristine, etoposide, prednisone, cyclophosphamide) and response-adapted radiation therapy (RT) - with RT use in a majority of pts. There remains room to improve outcomes in pediatric and adult pts with newly diagnosed advanced stage HL. The PD-1 pathway plays a critical role in the pathogenesis of HL and the disease is exquisitely sensitive to PD-1 blockade, as demonstrated in clinical trials of nivolumab and pembrolizumab in pts with heavily treated R/R HL. A phase II trial evaluating nivolumab combined with AVD (N-AVD) demonstrated promising safety and efficacy in pts with newly diagnosed HL. The incorporation of PD-1 blockade into front-line tx represents a clear opportunity to potentially improve the outcomes and tolerability of initial tx for pts with newly diagnosed advanced stage HL. A meeting was convened between the North American cooperative group Lymphoma Committee chairs, expert HL researchers and physicians, representatives from the Cancer Therapy Evaluation Program (CTEP), and patient advocates with the goals of harmonizing treatment approaches in advanced stage HL across pediatric and adult pts and reaching consensus regarding the optimal study design for a randomized trial incorporating PD-1 blockade into frontline tx for pts with advanced stage HL. Study champions were identified from each of the North American cooperative groups (SWOG, ECOG-ACRIN, Alliance, Canadian Cancer Trials Group, and Children's Oncology Group) and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes were included in the study team. The resulting clinical trial - S1826, led by SWOG Cancer Research Network - represents the largest advanced stage HL study in the history of the North American cooperative groups and the first prospective collaboration between COG and the adult cooperative groups in HL. S1826 (NCT03907488) is a randomized, phase III study of N-AVD versus BV-AVD in pts with newly diagnosed advanced stage HL. Eligible pts must be 12 years or older and have stage III or IV HL. Pts are randomized 1:1 to receive 6 cycles of treatment with either N-AVD or BV-AVD. Pts randomized to BV-AVD are required to receive G-CSF prophylaxis for neutropenia. Pts are eligible to receive RT to residually metabolically active areas on the end of treatment (EOT) PET scan at the discretion of the treating investigator. Pts are stratified during randomization based on age, international prognostic score, and intention to use EOT RT. The primary endpoint is to compare the PFS in pts randomized to N-AVD versus BV-AVD. Secondary endpoints include overall survival, event-free survival, the EOT complete metabolic response rate, and the safety and tolerability of N-AVD compared to BV-AVD. Another key secondary endpoint will be a comparison of patient-reported symptoms and health-related quality of life (overall, fatigue, neuropathy) between the study arms. 940 eligible pts are expected to be accrued over 4 years with a total of 987 pts assuming an expected ineligible rate of 5%. The S1826 study represents an unprecedented effort across the North American clinical trial cooperative groups to improve the cure rate in advanced stage HL and harmonize treatment approaches across pediatric and adult pts. Figure Disclosures Herrera: Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Immune Design: Research Funding; Pharmacyclics: Research Funding. Rutherford:Heron: Consultancy; Regeneron: Research Funding; Juno: Consultancy; Dova: Consultancy; Genentech/Roche: Research Funding; AstraZeneca: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy, Research Funding; Kite: Consultancy; LAM Therapeutics: Research Funding; Seattle Genetics: Consultancy. Parsons:Seattle Genetics: Consultancy. Prica:astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria. Shipp:Ono Pharmaceutical: Honoraria; Celgene: Honoraria; Merck: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Bayer: Honoraria. Crump:Kite/Gilead: Consultancy; Roche: Consultancy; Servier: Consultancy. Kahl:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Research Funding. Leonard:Miltenyi: Consultancy; Roche/Genentech: Consultancy; BMS/Celgene: Consultancy; MEI Pharma: Consultancy; Gilead/Kite: Consultancy; Bayer: Consultancy; ADC Therapeutics: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; GenMab: Consultancy; Sutro: Consultancy; Karyopharm: Consultancy. Smith:Karyopharm: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Astellas: Consultancy; Portola Pharmaceuticals: Consultancy; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy.
50
Chai, K., Yq Ai, and Lw Jiang. "Phase II study of dendritic cell vaccination combined with recombinant adenovirus-p53 in treatment for patients with advanced pancreatic carcinoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3049. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3049.
Full textAbstract:
3049 Background: There are few choices of treatments for advanced pancreatic carcinoma (PC) due to the resistances to chemo- or radio-therapy. Immunotherapy based on dendritic cell (DC) vaccines and p53-based gene therapy are two promising therapeutic modalities. They also demonstrated favorable safety profiles. In this study, we compared the immunological and clinical response between DC vaccine therapy and DC vaccine combined with recombinant adenovirus-p53 (rAd-p53) gene therapy. Methods: Thirty-six patients with a stage IV pancreatic cancer, 21 men and 15 women with an average age of 56.2 years old, were included in this study and randomly assigned to two groups: 16 patients in DC group (DCG) and 20 in DC plus rAd-p53 group (DPG). The DCG patients received autologous antigen-loaded DC (antigen from isolated pancreatic cancer cells) and the DPG patients received both DC and rAd-p53. DC vaccines were injected intra-dermally once every week for 4 injections and rAd-p53 were given by intravenous injections once per 3 days for 5 times at a dose of 3 x 1012viral particles. The response, safety and peripheral blood lymphocyte subsets were investigated. Results: The post-treatment CD3+, CD3+CD4+, CD4+/CD8+ ratio of patients’ peripheral blood in both groups were increased. But the percent of CD4+CD25+ regulatory T cells were significantly decreases. In DPG, 5 patients had a partial response (PR) and 4 patients had stable disease (SD) according to the RECIST standard. The 3 and 3 DCG patients achieved a PR and SD, respectively. The disease control rates (PR+SD) were 45.0% and 37.5% for DPG and DCG, respectively. The 6-month overall survival rates were 50.0% and 43.8% for DPG and DCG, respectively. The median survival times were 6.8 and 5.5 months for DPG and DCG, respectively. Mild to medium grade fever was observed in most of the patients in the two groups. No serious adverse events were found. Conclusions: DC-based immunotherapy and p53 gene therapy are safe and appropriate treatments for patients with advanced pancreatic carcinoma. The combined treatments showed more beneficial results than the DC immunotherapy alone.