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1
Nzegwu, Martin A., and Aloy Aghaji. "Neuroblastoma Occurring in a 38-year Old Nigerian Man: A Rare Finding." Rare Tumors 1, no. 1 (July 1, 2009): 20–21. http://dx.doi.org/10.4081/rt.2009.e15.
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Neuroblastoma (NB) is a common malignancy in children, but rarely occurs in adults. Accepted unfavorable prognostic factors include age over one year, low histological grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. We report a 38-year old civil servant who presented at our urology clinic on the 21st of December 2007 with a six month history of right flank dull pain which was worse on walking and relieved by rest, hypertension and a large right retroperitoneal mass. Tumor resection revealed a grade III NB. Chemotherapy using a combination of vincristine, adriamycin and cyclophosphamide was started. Follow-up showed regression of the mass initially with a relapse after patient absconded for three months. He resurfaced with new masses and he had a repeat chemotherapy with disappearance of the masses and is currently undergoing further treatment. To our knowledge this is the only report of NB in an adult registered so far in Nigeria and perhaps the whole of Africa. Currently, there are no standard treatment guidelines for patients with NB in adulthood. This study emphasizes the need for a standard treatment regime for adult onset neuroblastoma and its recognition as a possible differential in intra-abdominal mass in adults.
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Kievit, Linda, Pia Kræmer, Stephen Hamilton-Dutoit, and Henning Grønbæk. "Adult Presentation of Noncirrhotic Portal Hypertension and Ascites following Treatment for Wilms’ Tumor in Childhood." Case Reports in Gastroenterology 12, no. 1 (February 1, 2018): 56–62. http://dx.doi.org/10.1159/000486389.
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A 37-year-old male, who at the age of 8 years had been treated for right-sided Wilms’ tumor with nephrectomy, radiotherapy, and chemotherapy, presented with noncirrhotic portal hypertension (NCPH), grade 2 esophageal varices, and ascites. A CT scan demonstrated hypoplasia of liver segments 2 and 3. A liver biopsy showed portal tract fibrosis without cirrhosis, with histological features of NCPH. Liver vein catheterization showed a normal portal pressure gradient of 5 mm Hg while spleen to hepatic vein pressure was 29 mm Hg. NCPH after therapy for Wilms’ tumor is described in children within the first few years after treatment. This is the first case report in which the patient first presented symptoms as an adult, many years after cancer treatment.
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Dayani, Mohamad Ali, and Azin Mirzazadeh. "Prevention of contrast-associated acute kidney injury in cancer patients undergoing radiologic investigation using contrast media; a short-review to current knowledge." Journal of Nephropathology 8, no. 4 (October 21, 2019): 43. http://dx.doi.org/10.15171/jnp.2019.43.
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Contrast agents are non-biologically active substances required for various diagnostic imaging procedures. Exposure to contrast materials, predispose some patients to renal disturbances entitled as contrast-associated acute kidney injury. Nephropathy of contrast medium is a deterioration of renal function which happens within 24 to 72 hours after iodinated contrast medium injection. Cancer individuals have several risk factors for contrast-associated acute renal failure, consisting of administration of chemotherapy regimen, which are mainly nephrotoxic, presence of diabetes or chronic renal failure, hypertension, taking of non-steroidal anti-inflammatory drugs, simultaneous use of nephrotoxic drugs, aminoglycosides, cisplatin, cyclosporine A or amphotericin B, increases the risk of contrast-associated acute renal failure. Similarly, age more than65 years old and anemia is an independent risk factor for contrast-associated acute kidney injury and also timing of CT within 45 days after last chemotherapy and low fluid intake, as the common risk factors in cancer individuals.
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Blaes, A., B. A. Peterson, D. Yee, and B. Virnig. "Do ACE-I protect against the development of doxorubicin cardiac toxicity?" Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 6623. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.6623.
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6623 Background: Doxorubicin (DOX), an anthracycline, has been associated with irreversible cardiotoxicity. Recently, newer agents such as angiotensin converting enzyme (ACE-I) inhibitors have been used in small trials to prevent cardiac toxicity in patients receiving DOX. This retrospective study analyzes whether ACE-I and other medications are protective in the development of DOX cardiomyopathy. Methods: Patients receiving DOX chemotherapy at the University of Minnesota Cancer Center who had two or more multigated blood pool imaging (MUGA) scan or echocardiograms performed were identified and reviewed. Patients who had at least a 10% drop in their ejection fraction (EF) to below the lower limits of normal (50%) or had an absolute decrease in EF of 15% or greater were identified and compared with those that did not have a decline in EF. Patient variables and the use of concurrent medications were compared between these two groups using logistic regression. Results: 350 patients received DOX chemotherapy between November 2004 and 2007. Of 142 patients who had two or more MUGA scans performed during the course of their therapy, 22 (15%) had a significant drop in EF. Median age was 52 years old (range 7–88). 85 (60%) were female. Cancer diagnosis was breast (n = 26), lymphoma (n = 92), and other (n = 25). The median baseline EF of all patients was similar (62% versus 63%). A stepwise variable selection retained two predictors significant at alpha = 0.1 in a logistic regression model: Age and ACE-I (p = 0.0252 and p = 0.0940, respectively). Adjusting for Age, the odds ratio for ACE-I is 0.267, suggesting that ACE-I has a protective effect, as it reduces the probability of a drop in EF. Cumulative DOX dose, obesity, hypertension, and history of tobacco use did not appear to be associated with a decline in ejection fraction. The use of beta-blockers, aspirin or statins did not appear to be associated with a decline in ejection fraction. Conclusions: DOX chemotherapy has been associated with the development of cardiomyopathies. While this is an observational study that is limited by its retrospective nature, the study supports our hypothesis that the use of ACE-I is possibly protective when given with DOX chemotherapy and warrants further investigation. No significant financial relationships to disclose.
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Chavez-MacGregor, Mariana, Ning Zhang, Thomas A. Buchholz, Yufeng Zhang, Jiangong Niu, Linda Elting, Benjamin D. Smith, Gabriel N. Hortobagyi, and Sharon H. Giordano. "Trastuzumab-Related Cardiotoxicity Among Older Patients With Breast Cancer." Journal of Clinical Oncology 31, no. 33 (November 20, 2013): 4222–28. http://dx.doi.org/10.1200/jco.2013.48.7884.
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Purpose The use of trastuzumab in the adjuvant setting improves outcomes but is associated with cardiotoxicity manifested as congestive heart failure (CHF). The rates and risk factors associated with trastuzumab-related CHF among older patients are unknown. Patients and Methods Breast cancer patients at least 66 years old with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005 and 2009, and treated with chemotherapy were identified in the SEER-Medicare and in the Texas Cancer Registry–Medicare databases. The rates and risk factors associated with CHF were evaluated. Chemotherapy, trastuzumab use, comorbidities, and CHF were identified using International Classification of Diseases, version 9, and Healthcare Common Procedure Coding System codes. Analyses included descriptive statistics and Cox proportional hazards models. Results In total, 9,535 patients were included, of whom 2,203 (23.1%) received trastuzumab. Median age of the entire cohort was 71 years old. Among trastuzumab users, the rate of CHF was 29.4% compared with 18.9% in nontrastuzumab users (P < .001). Trastuzumab users were more likely to develop CHF than nontrastuzumab users (hazard ratio [HR], 1.95; 95% CI, 1.75 to 2.17). Among trastuzumab-treated patients, older age (age > 80 years; HR, 1.53; 95% CI, 1.16 to 2.10), coronary artery disease (HR, 1.82; 95% CI, 1.34 to 2.48), hypertension (HR, 1.24; 95% CI, 1.02 to 1.50), and weekly trastuzumab administration (HR, 1.33; 95% CI, 1.05 to 1.68) increased the risk of CHF. Conclusion In this large cohort of older breast cancer patients, the rates of trastuzumb-related CHF are higher than those reported in clinical trials. Among patients treated with trastuzumab, those with cardiac comorbidities and older age may be at higher risk. Further studies need to confirm the role that the frequency of administration plays in the development of trastuzumab-related CHF.
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Plotkin, Scott, James Tonsgard, Nicole Ullrich, Jeffrey Allen, Jaishri Blakeley, Girish Dhall, Jian Campian, et al. "CTNI-10. MAINTENANCE CHEMOTHERAPY USING BEVACIZUMAB FOR NEUROFIBROMATOSIS 2 PATIENTS WITH HEARING LOSS AND PROGRESSIVE VESTIBULAR SCHWANNOMAS: AN NF CLINICAL TRIALS CONSORTIUM STUDY (NF104)." Neuro-Oncology 22, Supplement_2 (November 2020): ii43. http://dx.doi.org/10.1093/neuonc/noaa215.177.
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Abstract BACKGROUND Bevacizumab treatment at 2.5–5 mg/kg/week is associated with hearing improvement and tumor shrinkage in about 40% of patients with neurofibromatosis 2 (NF2) and progressive vestibular schwannomas (VS). Treatment-emergent hypertension and proteinuria are common with prolonged treatment, and data supporting strategies to maintain hearing and minimize toxicity are lacking. METHODS We conducted a multicenter, phase II, open-label study of bevacizumab for subjects (≥6 years old) with NF2, hearing loss, and progressive VS. After 6 months of induction therapy (10 mg/kg every 2 weeks), subjects received low dose bevacizumab at 5 mg/kg every 3 weeks during maintenance therapy (18 months). Hearing decline was defined as a significant decrease in word recognition score below baseline. Progressive disease was defined as ≥20% increase in tumor volume from baseline. RESULTS Twenty of 22 subjects (median age=23 years) were treated with maintenance bevacizumab. The proportion of subjects free from hearing decline at 6, 12, and 18 months was 88%, 94%, and 85%, respectively; the proportion free from tumor progression at 6, 12, and 18 months from baseline was 88%, 94%, and 85%, respectively. Three subjects (15%) experienced hearing loss during maintenance and required dose escalation. Maintenance chemotherapy with bevacizumab was well tolerated: 1 subject discontinued due to perirectal abscess and 2 discontinued by choice. Grade 3 hypertension occurred in 2 subjects (10%). Adverse events of interest included hypertension (55%), proteinuria (20%), and irregular menstruation (6/13, 46%). CONCLUSIONS Maintenance chemotherapy with bevacizumab at 5 mg/kg every 3 weeks is associated with prolonged hearing and tumor stability that surpasses historical controls. A minority of subjects require dose escalation during low dose bevacizumab treatment.
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Rusu, Maia, Tudor Constantinescu, and Ruxandra Jurcuţ. "The Story of a Stone Heart – Another Side of Cardiooncology." Internal Medicine 16, no. 6 (December 1, 2019): 73–75. http://dx.doi.org/10.2478/inmed-2019-0095.
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AbstractA 38-year-old man was admitted to our department with moderate exertional dyspnea, fatigue and a syncope during exercise. The medical history revealed: left pulmonary sarcoma at the age of four, treated with radiotherapy, chemotherapy and left total pneumonectomy. At admission, laboratory tests showed high BNP (1426 pg/ml), normal calcium and parathormon levels. The transthoracic echocardiography found normal left ventricular (LV) systolic function with severe calcifications of the papillary muscles, mitral annulus, apical segments of the inferior septum and inferior wall (panel A - arrows; panel D) associated with severe mitral regurgitation (panel B). It also revealed severe tricuspid valve regurgitation, severe pulmonary hypertension (estimated to 120 mmHg, panel C) and small amount of pericardial fluid. A thoracic computed tomography described severe cardiac calcifications (panels E and F, arrow), a hypertrophic right lung herniated in left hemythorax and no other pathological findings in the remnant lung tissue. The pneumological evaluation noted a severe restrictive dysfunction. In this case, pulmonary hypertension was most probably determined by the left cardiac disorders (severe mitral regurgitation postradiotherapy, LV diastolic dysfunction due to severe myocardial and papillary muscle calcifications), most probably related to thoracic radiotherapy during childhood.
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Varela Almanza, K. M., A. M. Puebla-Perez, J. I. Delgado-Saucedo, F. Rodriguez-Arevalo, G. M. Zuniga-Gonzalez, L. E. Figuera, A. Moran-Mendoza, and M. P. Gallegos-Arreola. "INCREASED HOMOCYSTEINE PLASMA LEVELS IN BREAST CANCER PATIENTS OF A MEXICAN POPULATION." Experimental Oncology 40, no. 2 (June 22, 2018): 114–18. http://dx.doi.org/10.31768/2312-8852.2018.40(2):114-118.
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Aim: Hyperhomocysteinemia has been associated with different pathologies, including cardiovascular diseases, hypertension, diabetes, and breast cancer (BC). To examine the differences in total homocysteine (tHcy) plasma levels, we compared healthy women to BC patients from a Mexican population. Materials and Methods: The tHcy plasma levels were measured using high-performance liquid chromatography with a fluorescence detector in 89 female controls and 261 BC patients. Results: The observed plasma tHcy levels were significantly higher among the BC patients (11.1019 ± 5.9161 µmol/l) compared to the controls (9.1046 ± 1.3213 µmol/l) (p = 0.002), and these differences were evident when stratified by age (≥ 50 years old), menopause status, overweight and obesity, miscarriages, node metastases, progression, subtype classification (luminal, Her2 and triple negative) and nonresponse to chemotherapy. Conclusions: The tHcy plasma levels could be a good marker for the progression and chemosensitivity of BC in the analyzed sample from a Mexican population.
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Wen, Lu, Shukui Qin, Jin Li, Wenying Deng, Junsheng Wang, Guifang Zhang, Haijun Zhong, et al. "Safety and efficacy of apatinib in elderly patients with advanced or metastatic gastric cancer in the post-marketing phase IV study: Subgroup analysis by age (Ahead-G201)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 126. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.126.
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126 Background: Old age is a potential negative predictor, and thus is of interest. Data from the ongoing post-marketing Phase IV trial were collected to assess the effect of age on apatinib treatment in 2000+ patients (pts) with chemotherapy-refractory advanced or metastatic gastric cancer. Methods: This subgroup analysis was stratified by age (<65 or ≥65 yrs). Both incidence of adverse events (AEs) and clinical outcomes were compared. Results: 725 pts <65 yrs and 312 pts ≥65 yrs were enrolled (data cut-off 2017/7/10). Differences in gender, ECOG PS, BMI, disease duration and metastatic sites were observed. 68.6% and 39.7% of pts aged ≥65 yrs experienced AEs of any grade and grade ≥3, which were not different with 70.2% and 40.0% of pts aged <65 yrs. The common AE profile was similar, but elderly pts had a higher incidence of hypertension, diarrhea and bilirubin increase (Table). Pts ≥65 yrs showed a higher objective response rate (12.2% vs. 9.9%) and longer overall survival (7.82 vs. 6.05 mos); however, there was no statistical difference. The disease control rate (79.6% vs. 65.4%; p=0.002) and progression free survival (PFS) (5.71 vs. 3.22 mos; p<0.001) of pts ≥65 yrs were significantly superior to pts <65 yrs. Multivariate Cox regression model confirmed that age ≥65 yr was a positive prognostic factor for PFS independent of baseline and treatment characteristics (HR: 0.67 [95%CI, 0.50–0.88]). Conclusions: Pts ≥65 yr is not at increased risk of overall AEs, but hypertension, diarrhea and bilirubin increase should be closely monitored. The PFS benefit in elderly pts will be validated. Clinical trial information: NCT02426034. [Table: see text]
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Scalfani, Michael T., Paul M. Arnold, and Karen K. Anderson. "Metastatic adrenal pheochromocytoma to the thoracic spine." Coluna/Columna 9, no. 3 (September 2010): 343–46. http://dx.doi.org/10.1590/s1808-18512010000300017.
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To report on a case of pheochromocytoma metastases to the spine occurring more than 20 years after initial diagnosis. A 34-year-old female with a history of metastatic pheochromocytoma diagnosed at age 12 presented with weakness, heart palpitations, and circumferential back pain of five months duration. The patient had undergone multiple laparatomies for abdominal and hepatic metastases. Work-up revealed a destructive lesion at T9. After two weeks of preoperative phenoxybenzamine to control her hypertension, she underwent decompression, posterior fixation and fusion. Surgical intervention was followed by radiation therapy, zoledronic acid, and only one cycle of chemotherapy due to intolerance of side effects. The patient survived 25 years after original diagnosis, which far exceeds the average survival of less than 15 years. The patient died 26 months postoperatively due to progression of disease. Pheochromocytoma with spine metastases occurring more than 20 years after diagnosis is very uncommon, and should be considered in the differential diagnosis of a patient with a history of pheochromocytoma.
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Jain, Prantesh, Jahir Gutierrez Bugarin, Avirup Guha, Chhavi Jain, Tingke Shen, Ilya Stanevich, Seunghee P. Margevicius, et al. "Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15100-e15100. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15100.
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e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]
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Lafaras, Christos, Eudokia Mandala, Eugenia Verrou, Dimitrios Platogiannis, Kostas Zervas, Theodoros Bischiniotis, and George Ilonidis. "Pulmonary Hypertension after Thalidomide Administration in Multiple Myeloma Patients. Pilot Study." Blood 110, no. 11 (November 16, 2007): 4846. http://dx.doi.org/10.1182/blood.v110.11.4846.4846.
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Abstract Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects and endothelial damage. Thalidomide is effective (anti-inflammatory, immunomodulatory and anti-angiogenic) both in advanced MM and as first-line therapy in combination with dexamethasone or other cytotoxic chemotherapy. It has been associated with an increased risk of thromboembolic pulmonary hypertension (PH). PH in the absence of thromboembolism has been also described in MM patients during thalidomide treatment. Aim: detection of clinical and subclinical PH in MM patients after thalidomide treatment. 82 patients, 46–82 years (median age 61), 41 females, were studied. They underwent echocardiographic study at baseline, one month thearafter, six months later and whenever symptoms indicating deterioration of cardiac function were appeared. Echocardiographic signs of PH were especially identified: Right atrial and ventricular enlargement, hypokinesia or hypertrophy, systolic flattening of intraventricular septum as a result of the right ventricular pressure overload, pulmonary artery dilatation and septal displacement. Doppler echocardiographic quantitation of systolic arterial PH was obtained by measuring velocity of the tricuspid regurgitant jet using the Bernoulli formula and summing central venous pressure evaluated by inferior vena cava diameter and its alteration during inspiration as it enters right atrium. Clinical and echocardiographic evaluation revealed four patients (4/82, 4.87%) with PH. One patient had clinical signs and symptoms of right heart failure three months after thalidomide administration with progressive deterioration. He was a 59 year- old man with multiple myeloma IgG λ and 85% diffuse bone marrow infiltration. Echocardiogram performed at baseline, revealed mild aortic regurgitation due tocalcification of non coronary cusp, good biventricular function, mild left ventricular hypertrophy, diastolic dysfunction of impaired relaxation, no evidence of PH and no signs of amyloid cardiac infiltration. He had no history of obstructive pulmonary disease and his functional status was Class I (NYHA). The second patient was a 62 years old woman with IgG κ MM. Echocardiogram at baseline identified good biventricular function and left ventricular diastolic dysfunction of impaired relaxation. Echocardiogram six months after thalidomide administration detected mild pulmonary hypertension without clinical symptoms of functional status deterioration. Her medical history was unremarkable except for arterial hypertension. The other two patients (72 and 76 years) had coronary artery disease and developed subclinical PH 1 and 3 months after thalidomide administration. A significant corelation between structural heart disease, age and PH was observed. Nonimaging (plasma D-Dimer,ECG) and imaging (chest roentgenography, lung scanning and chest computed tomography) diagnostic methods excluded deep venous thrombosis and pulmonary embolism. Vascular involvement seems to be a plausible mechanism in the pathophysiology of PH. Pre-existed endothelial dysfunction due to structural cardiac disease enhances the vasoactive substances release (nitric oxide, endothelin) causing increased pulmonary vascular resistance. Thalidomide causes a vasodilator and vasoconstriction impalance which may cause abnormal pulmonary vascular response interfering to a vicious circle perpetuating PH.
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Urun, Y., G. Utkan, B. Yalcin, H. Akbulut, H. Onur, D. G. Oztuna, F. C. Senler, A. Demirkazık, and F. Icli. "THE ROLE OF CARDIAC BIOMARKERS AS PREDICTORS OF TRASTUZUMAB CARDIOTOXICITY IN PATIENTS WITH BREAST CANCER." Experimental Oncology 37, no. 1 (March 22, 2015): 53–57. http://dx.doi.org/10.31768/2312-8852.2015.37(1):53-57.
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Aim: Identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy. Materials and methods: Fiftytwo women with HER2+ breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken. Results: The median age was 48.5 year (range: 26–74). Hypertension and obesity were two most common co-morbidities. The median duration application of trastuzumab was 52 weeks. During median 14.5 (3–33) months follow-up cardiac adverse events occurred in 5 (9.6%) patients and 2 out of 5 was grade III–IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0.004) and diabetes mellitus (p = 0.002) between patients with and without cardiotoxicity. Conclusion: Although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.
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Shimada, Mitsuo, Tomohiro Nishina, Jun Higashijima, Toshikazu Moriwaki, Toshiki Masuishi, Yoshinori Sakai, Mitsuharu Ozeki, et al. "Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study)." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 588. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.588.
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588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.
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Lemez, Petr, Jirina Galikova, Kyra Michalova, Alan MacWhannell, Zuzana Zemanova, and Jan Stejskal. "Standard Dose Chemotherapy 3+7 Induces Complete Remission in Patients Over 80 Years Old with Single-Lineage Acute Myeloid Leukemias and Normal Karyotype." Blood 112, no. 11 (November 16, 2008): 4006. http://dx.doi.org/10.1182/blood.v112.11.4006.4006.
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Abstract Survival of elderly patients with de novo acute myeloid leukemia (AML) is poor. A single published study on patients with AML aged 80 years and above (DeLima et al., Br. J. Haematol.1996; 93: 89) concluded that chemotherapy was not indicated since median overall survival (OS) of 29 treated patients was 1 month, 9 patients reached complete remission (CR) of 3 months median duration, and only two survived over 1 year: for 15.5 and >18 months. The aim of our study was to identify the characteristics of elderly AML patients who may reach CR by standard chemotherapy. We analyzed 9 consecutive patients with de novo AML aged 80–90 (median 83) years treated by us in 1992–2007. All bone marrow films were hypercelullar with 48–92 (median 80) % leukemic cells, classified as FAB types: 2 M2, 6 M4, and 1 M5. Six patients, all with hypertension and five with ischaemic heart disease (IHD), received chemotherapy, while 3 patients (82–87 years old) opted for supportive or palliative therapy and survived 1–4 months. Cytosine arabinoside (Ara-C) 100 mg/sqm/12 h in 3-h infusion for 7 days and 3 doses of daunorubicin (DNR) 45 mg/sqm/d i.v. (D+A, 1 case) or mitozantrone (MTZ) 10 mg/sqm/d i.v. (M+A, 3 cases) was given to 4 patients. The remaining two patients received D+A with thioguanine (TG) 100 mg/sqm/12 h p.o. for 7 days (TAD). Their WHO performance status (PS) was 4x PS3, 1x PS2, 1x PS1, and median WBC 58 (17.9–97.8) × 10^9/L. Three patients with AML M4 and normal karyotype reached CR. Maintenance therapy consisted of 4-day courses administered in intervals of 5–12 (median 8) weeks according to the patient’s clinical status and tolerance until relapse. Courses containing Ara-C 60 mg/sqm/12h s.c. with TG 70 mg/sqm/12h p.o. were repeated 3x. The fourth course was 1+4 containing a single dose DNR or MTZ as described and Ara-C. The outcomes: An 85 year-old female with IHD and LVEF 25 % reached CR with TAD. She was on maintenance in CR for 17 months when severe heart arrhythmia developed. She refused a pacemaker implantation and died 3 days later. Her OS was 18.6 months. An 80 year-old male reached CR with M+A and was on maintenance therapy when relapsed after 19.7 months. He refused further chemotherapy and his OS was 28 months. An 80 year-old female (PS1, Flt3-ITD neg.) reached CR after D+A 3+7 and got one cycle D+A 2+5 without further maintenance. Her CR lasted 10.1 months. She was further treated with 2 cycles of low-dose Ara-C and her OS was 16.5 months. Three other patients, two with normal karyotype, did not reach CR after chemotherapy. A 90 year-old male with AML M4 died of mycotic pneumonia on the 24th day of TAD induction. An 83 year-old male with AML M5, PS2, experienced nonQ myocardial infarction after M+A induction and did not reach CR. He was further treated with hydroxyurea with OS of 2.7 months. An 80 year-old female with AML M2, complex karyotype, renal insufficiency and sepsis died after 7th hemodialysis in septic shock on 10th day of M+A induction. All three patients who reached CR did not exhibit dysplasia in erythroblastic or megakaryocytic lineage showing that only granulocyte-macrophage lineage was involved in the leukemic clone (single–lineage AMLs). In contrast, all 3 patients who did not reach CR exhibited megakaryocytic dysplasia in a half or more of megakaryocytes and two had erythroblastic dysplasia in more than 26% erythroblasts. They represent a different biological category of AMLs with multi-lineage involvement. In summary, we defined a biological category of single-lineage AML patients over 80 years of age who may benefit from standard dose chemotherapy in spite of their poor performance status.
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Agila, Amal R., Yousef Elgitait, and Mohamed Elawayeb. "Cancer Magnitude in West Libya and Study the Effect of Dietary Habits in Cancer Incidence and Cancer Treatment Using Nanotechnology." International Journal of Research in Science 1, no. 2 (September 15, 2015): 6. http://dx.doi.org/10.24178/ijrs.2015.1.2.06.
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This study provides an overview of magnitude of cancer incidence in West Libya form 2009 to 2013, to identify the role of bad meal in developing cancer, and to suggest further nano-technology research for treating cancer. Among 1851 cancer cases, 1472 cases (79.5%) occur in people aged above 40 years old. The most affected age by cancers was in males aged 61-70 years and in females aged 41-50 years. Lung cancer is the principal cancer in men accounting for 21% of cases, while breast cancer is the leading malignancy in women accounting for 35% of cases. Among 100 interviewed males and females with colon, stomach and liver cancers, 50% of them were eating a lot of red meat, canned and fast foods, whereas 20% of all cases were eating a little of fruits and vegetables. 22% of all cases were more likely to have a positive family history of cancer and 8% of all cases had chronic diseases such as diabetes, hypertension, urinary tract infection and gastritis. Good efforts have been made to improve the treatment of cancer by using nanomedicines in order to enhance the performance of chemotherapy and reduce systemic side effects.
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Jayarajah, Umesh, D. M. Hilary Fernando, Kasun Bandara Herath, M. V. Chandu de Silva, and S. A. S. Goonewardena. "Primary Signet-Ring Cell Adenocarcinoma of the Urinary Bladder Treated with Partial Cystectomy: A Case Report and Review of the Literature." Case Reports in Urology 2017 (2017): 1–4. http://dx.doi.org/10.1155/2017/6829692.
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Primary signet-ring cell carcinoma is a variant of adenocarcinoma which is extremely rare, associated with poor prognosis and generally found to be resistant to chemotherapy and radiotherapy. We report a case of primary signet-ring cell carcinoma of the bladder which was successfully treated with partial cystectomy. A 71-year-old female with a history of type 2 diabetes, hypertension, and ischaemic heart disease presented with painless haematuria for 2 months’ duration. The abdominal ultrasonography showed a localised polypoidal vesical growth arising from the bladder dome. Cystoscopy revealed an exophytic solid tumour in the anterior fundal wall. A deep transurethral resection of bladder tumour was done and histology revealed an adenocarcinoma composed of mucinous and signet-ring cell components. Later, considering the patient’s age and the poor general condition, a partial cystectomy was done. Follow-up cystoscopy and ultrasonography were done at 12 months and there was no evidence of tumour recurrence and the patient is currently symptom-free. Partial cystectomy may be considered in patients with localised tumour without evidence of metastasis and poor general condition. Regular cystoscopies and ultrasound imaging are necessary for follow-up and early identification of recurrences.
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Oukkal, M., F. Kara, S. Difi, D. Bouzidi, K. Bentabak, A. Graba, N. Smail, N. Ait Kaci, R. Baba Ahmed, and K. Bouzid. "Bevacizumab plus FOLFOX7 as first line treatment in patients with advanced colorectal cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e15092-e15092. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15092.
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e15092 Background: Bevacizumab a monoclonal antibody against vascular endothelial growth factor (VEGF) has shown in combination with chemotherapy a significant survival improvement in pts with advanced colorectal cancer (F. Kabbinavar JCO 2005 and H. Hurwitz NEJM 2004). In this study we investigated the safety and the efficacy of the addition of bevacizumab to FOLFOX7 regimen in pts with metastatic colorectal cancer. Methods: Inclusion criteria: Histological proven colorectal carcinoma, measurable disease at time of inclusion, no prior chemotherapy (adjuvant chemotherapy allowed), no CNS metastasis, no peripheral neuropathy, no other serious concomitant illness, ECOG PS ≤ 2, Urine dipstick of proteinuria <2+, adequate renal and liver function, good bone marrow reserve and informed consent. Pts received bimonthly Oxaliplatin 130 mg/m2 D1, Folinic acid 400 mg/m2 D1, Fluorouracil 2400 mg/m2 46 hours continuous infusion and Bevacizumab 5mg/kg D3 Results: From April 2005 to June 2007, 47 pts (M/F = 28/19, colon/rectum = 28/19) were enrolled in the study. Median age is 52,7 years old (32–74). They received 452 cycles, median=7 range (1–18). All pts were evaluable for toxicity and survival and 46 for responses. Complete response (CR) was achieved in 3 pts (6.6%), partial response (PR) in 28 pts (60.8%), stable disease in 4 pts (8.7%) and progressive disease in 11 pts (24%). The overall response rate (ORR=CR+PR) is 67.3%. Severe toxicity (CTC/NCI ¾ Grade) related to chemotherapy was neuropathy 5.3%, neutropenia 8.4%, anaemia 3.3%, thrombocytopenia 1.8%, vomiting 8.2%, diarrhoea 2.9%, stomatis 4.9% and allergy 0.7%. Toxicity related to Bevacizumab was bleeding CTCNCI grade 1 and 2 in 40.8%, hypertension grade 1 qnd 2 in 3.7% qnd grqde 3 in 0.2. proteinuria grade and 2 in 13.7%. 1 case of phlebitis and 1 case of Bevacizumab allergy Conclusions: Bevacizumab and FOLFOX7 combination is a promising treatment with high efficacy and safety profile for pts with advanced colorectal cancer No significant financial relationships to disclose.
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Zhu, Jay-Jiguang, Guangrong Lu, Mayank Rao, Ping Zhu, Nadine Linendoll, Xuejun Tian, Monika Pilichowska, et al. "NCMP-09. POSTMORTEM STUDY OF ORGAN SPECIFIC TOXICITY IN GLIOBLASTOMA PATIENTS TREATED WITH A COMBINATION OF TEMOZOLOMIDE, BEVACIZUMAB AND IRINOTECAN." Neuro-Oncology 22, Supplement_2 (November 2020): ii124—ii125. http://dx.doi.org/10.1093/neuonc/noaa215.521.
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Abstract Combined chemotherapy with temozolomide (TMZ), bevacizumab (BEV) and irinotecan (IRI) [TBI] has been used in patients with recurrent or progressive high-grade gliomas. Patients tolerated the regimen well with increased frequency of reversible clinical myelosuppression (CM), hypertension and proteinuria. However, organ-specific toxicities have never been evaluated by post-mortem examination. From 2009 to 2019, post-mortem examinations were performed in seventy-six decedents, including gliomas (N=68, 44/M and 24/F, median age: 59, ranging 23–80 years old) and brain metastases (N=8, 5/M and 3/F, ranging 39–75 years old). Twenty-four glioma subjects were treated with 1–25 cycles TBI (median 5.5) at glioma recurrence. All subjects’ clinical information, treatment histories and adverse events were collected. Five (7.7%, 5/65) glioma decedents (excluding three glioma patients who never received TMZ) permanently discontinued TMZ due to severe CM during concurrent chemoradiation therapy. There is no significantly elevated severity of CM from TBI when compared to standard of care therapies, nor when comparing extended TMZ treatment to the standard 12 cycles of TMZ. However, exposure to IRI significantly increased the CM occurrence (p< 0.05). Among glioma decedents, the most common cause of death was tumor progression (63.2 %, N=43), followed by aspiration pneumonia (48.5%, N=33). No deaths were attributed to acute toxicity from TBI. An electromicroscopic (EM) examination was performed in addition to routine autopsy procedures to investigate the cause of hypertension and proteinuria frequently developing in patients received BEV therapy. Ultrastructural evidence of thrombotic microangiopathy was observed in the kidneys among BEV users; however, it is difficult to conclude such changes were related to BEV due to rapid autolytic changes and artifacts. CONCLUSION: IRI, not the extended use of TMZ, significantly increased the frequency of reversible CM in recurrent glioma patients. There are no unexpected adverse events or organ-specific toxicities detected among glioma decedents who received the TBI regimen.
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Qu, Xiaoyan, Yan Gu, Jianyong Li, and Lijuan Chen. "Clinical Analysis of Thromboembolism Associated with Lenalidomide-Based Regimens for Multiple Myeloma Patients." Blood 126, no. 23 (December 3, 2015): 5368. http://dx.doi.org/10.1182/blood.v126.23.5368.5368.
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Abstract Objective: To investigate and analyze the incidence, risk factors, prophylaxis and treatment of thromboembolism associated with lenalidomide-based regimens for multiple myeloma (MM) patients. Methods: 22 newly diagnosed / relapsed MM patients received lenalidomide-based regimes from May 2013 to May 2015 in our department. All diagnosis of thromboembolism were based on objective clinical symptoms, and confirmed by imaging (lower extremity vascular ultrasound, chest CT angiography (CTA), and two-dimensional echocardiography). Investigatethe incidence of thethromboembolism, and analyze the prophylaxis and treatment for the thromboembolism according to risk factors such as patients' characteristics, disease status, and therapy regimes. Results: Aspirin was used as thromboprophylaxis in 16 patients, low molecular weight heparin (LMWH) in 2 patients, and warfarin in 1 patient, while 3 patients received no thromboprophylaxis. There were 4 cases were diagnosedas thromboembolism with the incident of 18.2%. Threeof them were deep vein thrombosis (DVT), while 1 patient was combined withpulmonary embolism (PE), andthe rest one was found thromboembolism in the left atria. The chemotherapy regimes were lenalidomide plus dexamethasone (≤40mg qw). Other risk factors include: old age, male, immobility, central venous catheter (CVC), surgical history, hypertension, cardiovascularevent, IgG/IgA and light chain type, newly diagnosis, and erythropoietin (EPO). The management of thromboembolism included LMWH, warfarin, venous filter placement, adjustment of chemotherapy regimes and maintenance therapy of antithromboembolism. All the 4 patients were well managedat the last follow-up. Conclusion: Thromboembolism was one of the most common non-hematologic adverse events of lenalidomide-based therapy. Aspirin was an effective option for thromboprophylaxis. More cases will be observed for longer time to optimize further evaluations forantithromboticprophylaxes, which include risk stratification-based prophylacticstrategies, new predictors and specific assessment of all thromboprophylaxis options. Disclosures No relevant conflicts of interest to declare.
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Merli, Francesco, Stefano Luminari, Giuseppe Rossi, Caterina Mammi, Luigi Marcheselli, Isabel Alvarez, Alessandra Tucci, et al. "Outcome of Elderly Frail Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Prospectively Identified by Comprehensive Geriatric Assessment (CGA). Results From a Study of the Intergruppo Italiano Linfomi (IIL)." Blood 116, no. 21 (November 19, 2010): 1771. http://dx.doi.org/10.1182/blood.v116.21.1771.1771.
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Abstract Abstract 1771 Introduction: There are currently no validated methods to prospectively identify elderly patients with Diffuse Large B-cell Lymphoma (B-DLCL) fit enough to receive full-dose treatment. CGA is a multidisciplinary comprehensive evaluation of an old individual's functional status, comorbid medical conditions, psychological state, social support, nutritional status and a review of the patient's medications. Recently CGA has been proposed as an objective tool for supporting medical decisions; the purpose of the present study is to prospectively evaluate the outcome of elderly patients with DLBCL that are defined as “frail” according to CGA. Patients and methods: In 2003 the IIL started a clinical research program for investigating initial treatment of elderly patients with DLBCL. Patients' ability to undergo full dose chemotherapy was prospectively evaluated by means of CGA, in addition to staging procedures. Patients older than 65 years with newly diagnosed stage II-IV DLBCL were defined as “unfit” or “frail” in case of age > 80 years, impairment of Activity of Daily living (ADL) scale (score <6), three or more grade 3 or one grade 4 comorbidities, and the presence of geriatric syndrome. Fit patients were addressed to a randomized trial comparing two different chemoimmunotherapy regimens (R-CHOP vs R-miniCEOP) while unfit patients were to be treated according to physician judgment. Results: From 2003 to 2006, 334 elderly patient with DLBCL were prospectively registered in the study and underwent CGA assessment; 235 were considered fit and were then registered in the randomized trial. According to CGA, the remaining 99 patients were classified as “frail”. Clinical data were available in 94 frail patients. Fail patients had a median age of 78 (range 66–93), stage III-IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2–3 in 53%. Comparing frail vs. fit patients the two groups only differed in terms of age. Reasons for considering patients as unfit were older age (42%), comorbidity (46%), impaired ADL (32%) and geriatric syndrome (25%). Most common comorbidites were hypertension (34%), heart disease (34%), diabetes (16%), and respiratory disease (15%). The most frequent inability was that referred to bathing (28%), dressing (23%), and toileting (17%); among the recorded geriatric syndromes the most frequent were depression (16%) and incontinence (14%). Treatment data were available for 82 frail patients and consisted of several different regimens; interestingly 67% received doxorubicin-containing regimens, 19% received combination without doxorubicin, and the remaining 14% were treated with single agent chemotherapy, radiotherapy alone or palliation. Combination chemotherapy was associated with rituximab in 32 patients (39%). Overall, 62 patients died; of these, 37(60%) died as a result of lymphoma progression and 15 (20%) for treatment-related complications/toxicity. After a median follow-up of 36 months for alive patients, 5-year Overall Survival (OS) was 28%. In multivariate analysis, aaIPI 2–3 (HR 1,5; P=0.001) and the presence of respiratoy comorbidity (HR=2.74: P=0.015) were the only factors that showed independent correlation with OS. When patients were stratified by treatment modality, those treated with rituximab containing combination chemotherapy had a better outcome (3 year OS = 44%) than patients treated with combination chemotherapy only (3 year OS = 24%). Finally, the outcome of frail patients was poorer than that of “fit” patients, as demonstrated by an HR of 3.03 (IC95% 2.17– 4.23; P<0.001). Frail patients had a poorer outcome compared with the “fit” ones also if they were treated with rituximab containing combination chemotherapy (HR 2.34 IC95% 1.43 – 3.83; P=0.001). Conclusions: Treatment of frail patients with DLBCL is largely unsatisfactory also if a treatment with curative intent is adopted. CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL. Respiratory disease and poor aaIPI are the most important prognostic factors for predicting OS of frail patients with DLBCL. Regimens containing rituximab seem to improve the outcome but clinical trials specifically addressed to this population are warranted. Disclosures: No relevant conflicts of interest to declare.
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Dsilva, Sehba, Gungor Karayalcin, and Sharon Singh. "Hodgkin Disease and Nephrotic Syndrome, a Rare Paraneoplastic Complication in Children with Literature Review." Blood 112, no. 11 (November 16, 2008): 4832. http://dx.doi.org/10.1182/blood.v112.11.4832.4832.
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Abstract The association between Hodgkin Disease (HD) and paraneoplastic Nephrotic Syndrome is well documented in adults but is relatively uncommon in the pediatric population. We describe two children with HD who initially presented with Nephrotic Syndrome. Case 1: 12- year-old boy who presented with a two-week history of periorbital edema, proteinuria and hypertension and was diagnosed with Nephrotic Syndrome. The renal biopsy showed minimal change disease. Since the patient developed dyspnea, further work-up was done and he was found to have a large mediastinal mass. Core needle biopsy of the mass was consistent with HD, nodular sclerosing type. Case 2: 14-year-old boy diagnosed to have Nephrotic Syndrome with biopsy proven minimal change disease and was treated intermittently with steroids over 6 months. He subsequently developed dyspnea and was found to have a right paratracheal mass and excisinal biopsy was consistent with HD, nodular sclerosing type. Both these patients initially presented with Nephrotic Syndrome which completely resolved after the first course of chemotherapy for HD. Upon review of literature, there have been 23 pediatric cases of Nephrotic Syndrome associated with HD in patients ranging in age between 2–15 years. The renal biopsy was not done for 8 of these patients and the diagnosis was established clinically. Fifteen patients had biopsies, 9 had minimal change disease, 1 mesangial hypercellularity, 1 glomerulosclerosis, 1 undetermined histology and 3 were normal. In all cases, the Nephrotic Syndrome was refractory to steroids and resolved with treatment of the HD. Pathogenesis of the Nephrotic Syndrome associated with HD is not known, however there are speculations about T-cell involvement and production of lymphokines and humoral factors which may be responsible for the glomerular damage.
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Prados, M., M. Gilbert, J. Kuhn, K. Lamborn, T. Cloughesy, F. Lieberman, V. Puduvalli, H. I. Robins, A. Lassman, and P. Y. Wen. "Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05–02)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 2005. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2005.
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2005 Background: Single agent targeted therapy has been disappointing in GBM. Combination therapy simultaneously targeting both EGFR and the MAP kinase pathway may be more effective. Methods: The NABTC conducted a phase I/II study of sorafenib (VEGFR/PDGFR/Raf inhibitor) in combination with erlotinib (EGFR inhibitor) in recurrent GBM. Eligibility criteria included histologically proven GBM, radiologic progression, > 18 yrs old, KPS > 60, adequate bone marrow reserve, and organ function. There was no limit on the number of prior therapies for phase I and no more than two prior relapses for phase II. No enzyme-inducing antiepileptic drugs were allowed. Dose-finding used a standard 3 + 3 design and the MTD was defined as the dose with DLTs in 1/6 or fewer patients. The primary endpoint for the phase II component was PFS6 (p0 = 15%; p1 = 35%). A 2-stage design was used. If > 4 of the initial 19 patients achieved PFS6, an additional 14 patients would be accrued for a total of 33 patients. Results: In phase I, 17 patients were enrolled. Median age 50 years (35–69); median prior chemotherapy 1 (1–3). The initial doses were sorafenib 200 mg bid and erlotinib 100mg qd. MTD was 400 mg bid of sorafenib daily combined with 100 mg of erlotinib daily. At this dose 1/6 evaluable patients had a DLT (grade 4 lipase). Other grade 3 or 4 toxicities included transaminitis, hypertension, hypophosphatemia, and increased lipase. Pharmacokinetic studies showed no alterations in sorafenib PK, but no accumulation of erlotinib, suggesting a drug-drug interaction with sorafenib altering erlotinib metabolism or clearance. In phase II, 19 patients were accrued to stage I. Median age 51 years (30–75); median prior chemotherapy 2 (range 1–3). Phase II toxicity and outcome data are not yet mature but will be available at the time of presentation. Conclusions: This combination was moderately well-tolerated. MTD was below other combination phase I studies. Sorafenib affected the PK of erlotinib preventing drug accumulation. Phase II toxicity and outcome data will be reported. [Table: see text]
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Hu, Nanlin, and Peng Yuan. "A phase II, single-arm study of apatinib and oral etoposide in pretreated metastatic HER2-negative breast cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1076. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1076.
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1076 Background: There is no standard treatment strategy for patients with locally advanced or metastatic breast cancer suffering progression after one prior chemotherapy with metastasis setting. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). Etoposide is a highly active chemo-drug in the treatment of advanced breast cancer, both as a single agent or in combination regimens, and is well tolerated, with a low incidence of severe toxicity. This study is performed to assessed the efficacy and safety of apatinib and oral etoposide in patients with HER2 negative locally advanced or metastatic breast cancer for whom at least one lines of prior chemotherapy had failed. Methods: This open-label, single arm study enrolled patients with HER2-negative breast cancer, pretreated with anthracycline, taxanes, and who failed in the metastatic setting at least one prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients. Apatinib was administered 425/500mg daily according to patients ECOG(Eastern Cooperative Oncology Group) status, oral etoposide was administered 50mg/m2 for first 10 days in a 21-days cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment duration is until disease progression or intolerability of apatinib or oral etoposide. Results: 20 eligible patients were enrolled in this, open-label, single arm study and received apatinib and oral etoposide with a median age of 54 years old(range 36 to 66 years). Median follow-up time was 11months. 20 patients were eligible for efficacy analysis. Median PFS was 5.6 months (95% confidence interval (CI), 4.01 m – 8.42 m). ORR was 20% (4/20). DCR was 70% (14/20). Median OS was 11.2 months (95% CI, 9.6 m – 14.95 m). The most common grade 3/4 treatment-related AEs were hypertension (30%), and proteinuria (5%), nausea (5%). 35%(7/20) patients had dose reduction because of adverse events, after that all adverse events can return to less than 2 grade. Conclusions: Apatinib with oral etoposide exhibited objective efficacy in pretreated, metastatic HER2-negative breast cancer with manageable toxicity. Prospective studies enrolling more patients are needed. Clinical trial information: NCT03535961.
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Huang, Xin, Zhaoming Ye, Tao Li, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, and Jia Chen. "A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft tissue sarcoma." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e23531-e23531. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e23531.
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e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.
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Ellis, Leslie R., and Steven M. Horwitz. "The Utility of Gemcitabine and Vinorelbine in Patients with Blastic NK Lymphoma (CD4+/CD56+ Hematodermic Neoplasm)." Blood 106, no. 11 (November 16, 2005): 4752. http://dx.doi.org/10.1182/blood.v106.11.4752.4752.
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Background: Blastic NK lymphoma, provisionally renamed CD4+/CD56+ hematodermic neoplasm in the latest WHO-EORTC classification of cutaneous lymphomas, is a rare, recently described malignancy. The derivation of these neoplasms is not completely understood, but it is felt to arise from either an NK or plasmacytoid dendritic cell precursor. Nonetheless, treatments for this aggressive malignancy have generally been in the form of intensive combination chemotherapy adapted from high-grade lymphoma or acute leukemia regimens. Despite initial responses to treatment, patients frequently relapse, with overall survival measured in months. Moreover, the high toxicity of these approaches limits their use in certain patients. Gemcitabine and vinorelbine are two chemotherapy agents with relatively mild side effect profiles and activity against cutaneous and T cell lymphomas. Here we describe two patients with blastic NK lymphoma who, because of advanced age and multiple comorbidities, received treatment with a combination of gemcitabine and vinorelbine (GN). For both patients, complete responses (CRs) were obtained. Patients and Methods: The first patient was a 73 year-old man with hypertension, recent hemorrhagic stroke with residual hemiparesis, and stable angina who presented with multiple cutaneous nodules along his face, trunk, and extremities. CT and PET scans were negative. Laboratories revealed pancytopenia, and bone marrow biopsy was negative although flow cytometry on the bone marrow aspirate showed increased CD56+ cells. The second patient was a 71 year-old male with poorly controlled diabetes and hypercholesterolemia; he also presented with extensive cutaneous nodules. CT and PET scans showed diffuse hypermetabolic lymphadenopathy; bone marrow was replaced by lymphoma. Skin biopsies from both patients showed large lymphoid cells expressing CD4, CD56, and HLA-DR; neither tumor expressed CD3, CD45RO, or TdT. Cytogenetics were normal for both patients. Results: Both patients received treatment with gemcitabine 800 mg/m2 and vinorelbine 15 mg/m2 given every two weeks with growth factor support. Both patients experienced significant improvement in their cutaneous lesions after the first cycle of treatment and subsequently obtained a CR by the fifth course. Once in CR, both patients had their chemotherapy schedules reduced to every four weeks to minimize side effects. The first patient had GN discontinued after 13 cycles and remained in CR for 10 months off therapy. He subsequently recurred in the skin, lymph nodes, and bone marrow. He was retreated with GN for an additional 14 cycles to date; he remains in CR nine months later on monthly therapy. The second patient developed recurrent disease in the skin at five months and was switched to alternate therapy. Conclusion: Blastic NK lymphoma (CD4+/CD56+ hematodermic neoplasm) is an aggressive lymphoma characterized by a poor prognosis and brief responses to intensive combination chemotherapy. Here we report two elderly patients with multiple comorbidities who responded to a mild chemotherapy regimen of GN given every two to four weeks. This regimen was well-tolerated and both patients attained a CR. The high activity in both patients and durability of response in one suggests GN should be considered for elderly patients with blastic NK lymphoma. Moreover, this report raises the possibility of incorporating these agents into other regimens for this rare disease.
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Murahashi, Satoshi, and Daisuke Takahari. "Case review for ramucirumab as a single agent in our hospital." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 52. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.52.
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52 Background: Ramucirumab is approved in the USA, EU, and Japan as second-line treatment in advanced gastric or gastroesophageal junction adenocarcinoma. This agent is often used with paclitaxel, but we can use it as a single agent in second-line treatment. Because REGARD trial has shown that Ramucirumab as a single agent prolongs overall survival and progression-free survival. However, this trial doesn’t include Japanese patients, and we have no trial concerning the efficacy of Ramucirumab as third or later-line treatment up to date. We reviewed retrospectively the efficacy and safety of Ramucirumab as a single agent in our hospital. Methods: We investigated 12 cases from June (when Ramucirumab has been approved) to September. Results: The median age was 61 years old, 6 male and 6 female patients. Performance status (0/1/2) = (1/10/1) cases. (second/third/fourth or later)-lines = (4/4/4) cases. Metastatic sites are lymph node, liver, lung, bone, and peritoneum. 7 patients had gastrectomy and 5 patients of them received adjuvant chemotherapy. Response rate is 50%, median progressive-free survival is 51 days, and median overall survival is 13 months. Some patients experienced grade 1or 2 adverse events: fatigue, loss of appetite, diarrhea, and hypertension. Conclusions: We cannot say that single agent administration of Ramucirumab demonstrates good response, some patients kept stable disease in this regimen. Ramucirumab as a single agent can be an option of treatments after paclitaxel fails or when it is difficult to administrate it.
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Lee, Young Kyung, Miyoung Kim, Hyo Jung Kim, Hyun Lim, and Hyo Geun Choi. "Increased Risk of Lymphoid Malignancy in Patients with Herpes Zoster: A Longitudinal Follow-up Study Using a National Cohort Study." Blood 132, Supplement 1 (November 29, 2018): 976. http://dx.doi.org/10.1182/blood-2018-99-113217.
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Abstract Introduction: A causal relationship between viral infection or decreased immunity and certain types of lymphoid malignancy has already been established. We performed a matched-control prospective follow-up study from a nationwide population-based dataset in South Korea to explore the association between herpes zoster exposure and the subsequent risk of lymphoid malignancies. Methods: Data in the Korean National Health Insurance Service-National Sample Cohort were collected from 2002 to 2013. We extracted the data of herpes zoster participants (n = 64,152) and their matched controls at a ratio of 1:4 (n = 1,061,539) and analyzed the occurrence of lymphoid neoplasms. Herpes zoster was diagnosed as ICD-10 B02, among them, we selected the participants who were treated for it ≥ 2 times or who were treated with antiviral medication ≥ 1 time. Lymphoid neoplasms were included using ICD-10 codes C81, C82, C83, C84, C85, C88, C90, and C91. For accurate participant inclusion, we used claim codes to select participants who were treated for lymphoid neoplasm ≥ 3 times or who were treated with chemotherapy or radiation therapy (n = 1,399). The matches were processed for age, group, sex, income group, region of residence, and past medical histories (hypertension, diabetes, and dyslipidemia). In both the herpes zoster and control groups, participants with a history of hematologic malignancy (lymphoid malignancy and acute leukemia) before the index date were excluded. In the herpes zoster group, 198 participants were excluded. The herpes zoster participants for whom we could not identify enough matching participants were excluded (n = 420). We excluded participants who were under 20 years old (n = 4,039). Finally, 1:4 matching resulted in the inclusion of 59,495 herpes zoster participants and 237,980 control participants. However, they were not matched for ischemic heart disease, cerebral stroke, or a history of depression as such strict matching increases participant drop out the due to lack of control participants. The income groups were initially divided into 41 classes (one health aid class, 20 self-employment health insurance classes, and 20 employment health insurance classes). These groups were recategorized into 11 classes (class 1 [lowest income] - 11 [highest income]). Region of residence was divided into 16 areas according to administrative district in South Korea. The past medical histories of participants were evaluated using ICD-10 codes. For accurate diagnosis, the presence of hypertension (I10 and I15), diabetes (E10-E14), and dyslipidemia (E78) was checked if the participants were treated ≥ 2 times. Ischemic heart disease (I24 and I25) and cerebral stroke (I60-I66) were assessed if the participants were treated ≥ 1 time. Depression was defined using the ICD-10 codes F31 (bipolar affective disorder) through F39 (unspecified mood disorder) diagnosed by a psychiatrist ≥ 2 times. Results: The rate of lymphoid neoplasm was higher in the herpes zoster group (0.15% [90/59,495]) than in the control group (0.08% [212/237,980], P < 0.001). The general characteristics (age, sex, income group, region of residence, and hypertension, diabetes, and dyslipidemia histories) of the participants were exactly the same due to the matching (P = 1.000). The rates of a history of ischemic heart disease and depression were higher in the herpes zoster group (each P < 0.05). The crude and adjusted HRs for lymphoid neoplasm were 1.70 (95% CI = 1.33 - 2.17) and 1.69 (95% CI = 1.32 - 2.16) in the herpes zoster group, respectively (each P < 0.001). In the subgroup analyses, the crude and adjusted HRs for lymphoid neoplasm were higher in all herpes zoster groups (each P < 0.05). The adjusted HRs were 1.72 (95% CI = 1.18 - 2.50) for those < 60 years old, 1.66 (95% CI = 1.20 - 2.31) for those ≥ 60 years old, 1.76 (95% CI = 1.24 - 2.48) for men, and 1.62 (95% CI = 1.14 - 2.31) for women. Conclusion: Our study demonstrates that herpes zoster infection increases the risk of subsequent lymphoid malignancies irrespective of age and gender in the Korean population. Disclosures No relevant conflicts of interest to declare.
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William, W. N., M. S. Kies, F. V. Fossella, G. Gladish, J. V. Heymach, B. S. Glisson, W. H. Tse, D. Liu, R. S. Herbst, and S. M. Lippman. "Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18098. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18098.
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18098 Background: The combination of bevacizumab, paclitaxel and carboplatin has been recently shown to increase response rates and survival in patients (pts) with untreated, metastatic, non-squamous, NSCLC and is currently FDA-approved for this indication. However, there are limited data on the safety and efficacy of bevacizumab in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open-labeled, phase II trial of bevacizumab, docetaxel and carboplatin for pts with NSCLC. Methods: Eligibility criteria included chemotherapy-naïve stage IIIB or IV incurable NSCLC of non-squamous cell histology, PS 0–1, no brain metastases, no history of hemoptysis, no cavitation, stable cardiac condition and no full dose anticoagulation. Treatment consisted of docetaxel 75 mg/m2, carboplatin AUC 6, and bevacizumab 15 mg/kg IV on day 1 every 3 weeks for up to 6 cycles followed by bevacizumab 15 mg/kg alone every 3 weeks until progression. The primary endpoint was progression-free survival. Results: 20 pts (12 females) have been enrolled with a planned sample size of 50 pts. Baseline characteristics were: median age 66 years old (37–77), PS 0 (6 pts) or 1 (14 pts), stage IIIB (1 pt) or IV (19 pts). 19 pts are evaluable for response and toxicity at this time. Severe adverse events (SAEs) included: 4 pts with neutropenia (2 febrile neutropenias), mild hemoptysis in 2 pts (treated with radiotherapy), 1 pt with peritoneal perforation (who had a history of diverticula), 1 pt with pulmonary embolism, and 1 pt with grade 3 hypertension. Partial responses by RECIST have been observed in 14 pts (74%, 13 confirmed), and stable disease in 5 pts (26%, 4 confirmed). Disease control rate (PR+SD) was 100% after 4 cycles of therapy. 9/20 pts are off treatment (3 progressions, 5 SAEs, 1 maximal benefit). Progression-free survival will be reported at the completion of the trial. Conclusions: The combination of bevacizumab, docetaxel and carboplatin appears to be efficacious and tolerable for the first-line treatment of metastatic NSCLC. No significant financial relationships to disclose.
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Bai, Chunmei, Diansheng Zhong, Ruixing Zhang, Xiubao Ren, Likun Liu, Nan Du, Junyan Yu, et al. "Prospective, multicenter, noninterventional and registry clinical study of apatinib in patients with advanced gastric cancer." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 137. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.137.
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137 Background: The aim of this study was to observe the safety of apatinib in the real world with wider inclusion criteria. The efficacy of apatinib was evaluated including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Methods: This trial enrolled patients from 32 centers in china with advanced gastric adenocarcinoma who had progressed after undergoing at least two lines of systemic chemotherapy, or patients who were considered to benefit from the treatment. We recommended starting from oral administration of 500mg qd, 28 days for a cycle. Dose could be appropriately adjusted according to the patients’ physical condition. Results: Between March 2015 and September 2017, 326 patients were enrolled. The average age was 62 years old, and the ratio of male to female was about 2:1. Patients received perioperative, first-line, second-line, and third-line or more treatment were 1,39,69 and 217 people respectively. There were 192 patients received efficacy evaluation, 9 patients achieved partial response(PR), 125 had disease stability(SD). The ORR and DCR were 4.6% and 69.8% respectively. The median PFS and median OS were 3.7 months and 7.3 months respectively. In the 326 patients, there were 153 patients with initial dose of 500 mg, 3 and 55 patients achieved PR and SD, respectively. The ORR and DCR were 3.3% and 63.7%, respectively. The median PFS and median OS were 3.5 months and 8.4 months, respectively. There were 237 patients in all 326 patients received safety analysis. Common adverse events were hypertension (57%), hand-foot skin reactions (26.6%), fatigue (29.5%), proteinuria (19.0%), bleeding (10.1%) and diarrhea (8.0%). The grade 3 to 4 adverse events were hypertension (6.3%), hand-foot skin reactions (3.8%), proteinuria(3.0%) and bleeding (2.1%). Conclusions: This real-world data in which more patients were given apatinib 500mg or less qd showed similar efficacy to Phase III clinical trial (850mg qd).The incidence of adverse events was consistent with that of Phase III clinical data,there was no new adverse events had been seen. Clinical trial information: NCT02668380.
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Wang, Chenchen, Mingzhu Huang, Qirong Geng, Wenhua Li, Jinjia Chang, Wei Tang, and Weijian Guo. "Apatinib for patients with metastatic biliary tract carcinoma refractory to standard chemotherapy: results from an investigator-initiated, open-label, single-arm, exploratory phase II study." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592110390. http://dx.doi.org/10.1177/17588359211039047.
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Background: There is no standard therapy for metastatic biliary tract carcinoma (BTC) refractory to first-line chemotherapy. Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an activity against BTC xenografts in preclinical models. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with metastatic BTC. Methods: This is a single-arm phase II study [ClinicalTrials.gov identifier: NCT03427242]. Eligible patients were aged 18 years or older; histologically confirmed metastatic BTC; refractory or intolerance to at least one chemotherapeutic regimen; no prior use of anti-angiogenic targeted drugs; Eastern Cooperative Oncology Group performance status of 0–2. Patients received oral apatinib 500 mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progress free survival (PFS). The secondary endpoint was overall survival (OS), objective response rate (ORR) and treatment safety. Results: A total of 22 patients were recruited. All of them received apatinib medication. The median age was 63 (44–75) years old. Twenty patients received efficacy evaluation after treatment. The objective response rate (ORR) and disease control rate (DCR) were 15.0% and 60.0%, respectively. The median PFS was 2.73 months [95% confidence interval (CI): 1.74–3.72 months], with 6 months PFS rate of 27.3% (95% CI: 8.7–45.9%). The median OS was 4.81 months (95% CI: 3.16–10.9 months), with 12 months OS rate of 36.4% (95% CI: 16.2–56.6%). Nine out of 22 patients (40.9%) had grade 3/4 adverse events. The most common grade 3/4 adverse events were hand-foot skin syndrome [three (13.6%) patients] and hypertension [two (9.1%) patients]. No treatment-related death occurred. Conclusions: For patients with metastatic BTC, apatinib showed an anti-tumor activity with acceptable safety, which deserves the further clinical trial. This trial was prospectively registered on ClinicalTrials.gov [NCT03427242]. Date of first patient enrollment: 26 January 2018. Date of registration (date of first posted): 9 February 2018.
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Kong, Tiandong, Lu Chen, Fangfang Duan, Xiaoxia Hou, Liuyan Wang, Hanli Zhou, Lanrong Wang, Shanshan Hu, and Danna Liu. "Efficacy and safety analysis of anlotinib combined with etoposide plus cisplatin/carboplatin as first-line therapy for extensive-stage small cell lung cancer (SCLC): The final results from a phase II single-arm trial." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 8560. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8560.
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8560 Background: In recent years, the therapeutic regimens of extensive-stage small cell lung cancer (ES-SCLC) have progressed a lot. The most significant clinical studies include IMpower133 and CASPIAN. However, the relevant results showed that the combination of PD-L1 monoclonal antibody and EC regimen chemotherapy as first-line treatment of small cell lung cancer have a median PFS (progession-free survival) of about 5 months, which is comparable to that of simple chemotherapy. Therefore, the EP/EC is still the standard treatment for extensive-stage small cell lung cancer. Meanwhile, we noticed that anlotinib (multi-target small molecule oral VEGF inhibitor) has a curative effect on patients with extensive-stage SCLC as a third-line or above treatment in the ALTER 1202 study in China. Therefore, we tried to add anlotinib to the first-line treatment with EP/EC regimen in patients with ES-SCLC to observe the efficacy and safety. Methods: Eligible ES-SCLC pts (18̃75 years old, initial treatment, no obvious heart, liver and kidney dysfunction) were received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) + etoposide(100mg/m2, d1̃3 of a 21-day cycle)+CBP (AUC = 4̃5,d1,Q3W) or DDP (70̃75mg/m2, d1,Q3W) for 4̃6 cycles, then anlotinib maintenance (12mg QD from day 1 to 14 of a 21-day cycle) until the disease progresses or intolerable adverse reactions occur. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The main observation endpoints were ORR, PFS and adverse events. Results: Between January 2019 and August 2020, a total of 20 patients with extensive-stage SCLC were enrolled in the study, with an average age of 66.2 ± 8.1(45-75) years old, 17 males (85%) and 3 females (15%). The median PFS was 10 months (95% CI: 7.809-12.191), median OS was 15 months (95%CI:10.639-19.361), ORR (objective remission rate) was 90% and DCR (disease control rate) was 100%. The most common grade 3 or 4 adverse events related to the trial regimen included: neutropenia was 10/20 (50.0%), thrombocytopenia was 5/20 (25.0%), anemia, nausea and fatigue were all 2/20 (10%), hypertension, transaminase elevation and hoarseness were all 1/20 (5%). Conclusions: Anlotinib combined with EP/EC regimen has better PFS, OS, ORR and DCR for the initial treatment of extensive-stage SCLC, and a manageable safety profile. A randomized, controlled phase III clinical study will be conducted to confirm this conclusion. Clinical trial information: ChiCTR2000035043.
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Xia, Ling, Yu Gao, Jun Gong, Jing Dai, Jin Peng, Lilin He, Weidong Chen, et al. "Apatinib in combination with docetaxel and S1 chemotherapy in the first-line treatment of metastatic gastric cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4055. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4055.
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4055 Background: First-line chemotherapy in metastatic gastric cancer, either doublet or triplet-regiment, the average OS is less than one year. Anti-VEGF target therapy is proven to be effective both in second and third line settings. As for apatinib, which is the tyrosine kinase inhibitor showed highly affinity for VEGFR2, is permitted by SFDA to be used in the third line treatment of gastric cancer since September 2014. The post-market stage IV clinic trial Ahead-G201 further confirmed it can improve the OS in chemotherapy-refractory gastric cancer. What’s more, apatinib could reverse paclitaxel resistance and improve the R0 resection rate in conversion of unresected gastric cancer in neoadjuvant settings. However, the safety and efficacy of apatinib in combination with docetaxel plus S1 in the first line treatment of metastatic gastric cancer is unknown and worthy of investigation. Methods: With expectation to improve PFS from 5.3m (the START Study) to 7m, this investigator-initiated, single arm, multi-center, registered phase II prospective study was designed to enroll 48 eligible patients diagnosed with metastatic gastric cancer. Each participant was expected to finish six cycles of chemotherapy plus apatinib (docetaxel 75mg/m2, d1, Q3W; S1 according to BSA: <1.25 40mg po bid; 1.25̃1.5 50mg po bid; >1.5 60mg po bid; d1-14, Q3W; apatinib 500mg po qd). The toxicity was determined according to CTCAE 4.0. Efficacy assessed every two cycles (6 weeks) during the study and every 2 months during the follow-up period. The primary endpoint was PFS. The secondary endpoint was OS, ORR, and DCR. The tumor response was determined according to RECIST 1.1 criteria. Results: Baseline characteristics (FAS population): From July 2017 to December 2020, 45 patients from 5 centers across Hubei province were enrolled. Among them, 44 are eligible for analysis. There are 15 females and 30 males, median age 55 years old, median metastasis sites is 2, yet 63.6% of them have involved at least 2 organs. Safety: 90.91% patients reported adverse events (AEs). The incidence of grade 3-4 AEs was 47.73%. Main 3-4 AEs were oral ulceration (13.64%), leucopenia (13.64%), neutropenia (13.64%), hand-foot syndrome (6.82%), hypertension (6.82%), and thrombocytopenia (6.82%). Efficacy: By Jan 31th, 2021, 44 patients were evaluable for response and survival, 26 of them achieved partial response (PR), 9 achieved stable disease (SD), and 8 experienced progression disease (PD). The ORR is 60.47%, the DCR is 81.4%. Median PFS is 7.46m, median OS is 12.42m. So we closed the study in advance. Conclusions: Adding apatinib to standard DS chemotherapy as the first line treatment would be well tolerant in patients with metastatic gastric cancer, the spectrum of toxicity were not exceeding expectation. This modality also exhibits prolonged PFS, which might provide an alternative therapeutic strategy for metastatic gastric cancer. Clinical trial information: NCT03154983.
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Addeo, R., V. Faiola, G. Cennamo, R. Guarrasi, L. Montella, P. Iodice, A. Sgambato, E. Capasso, M. Caraglia, and S. Del Prete. "A novel metronomic schedule of oral vinorelbine for the treatment of metastatic breast cancer in elderly patients: A phase II trial." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1085. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1085.
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1085 Background: Oral vinorelbine (VNR) is particularly useful in elderly patients due to its favorable toxicity profile. Several studies demonstrated that this drug seems to represent an active treatment for metastatic breast cancer (MCB). We evaluated the clinical efficacy and tolerance of metronomic chemotherapy with oral VNR. Methods: Women were eligible if they had a histologically proven untreated MBC and were > 70 years old. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have negative estrogen receptor status, at least one bidimensionally measurable target lesion, Karnofsky performance status >70; life expectancy > 3 months. Each patient received oral vinorelbine 80 mg/m2 fractionated in days 1, 3, and 5, three week on-one week off, every 4 weeks, for a maximum of six cycles unless disease progression or unacceptable toxicity. Results: Thirty-two patients with MBC were eligible, assessable for response, and toxicity. The median age was 75 years (range 70–84), sixteen patients (50%) had a Karnofsky performance status of 90–100. The main comorbidities recorded were: hypertension in 9 (28%) patients and diabetes mellitus in 6 (19%). The overall response rate (on an intent-to-treat basis) was 41% (13 of 32; 95% CI, 20%-54%). Two complete response and 11 partial responses were noted. In addition, other 10 patients (31%) had stable disease of > 4 months duration, and 9 patients (28 %) had disease progression. Median time to disease progression was 7.1 months and median overall survival was 12.7 months. The schedule was well tolerated, grade 3 toxicity was observed only in two patients. Conclusions: Metronomic oral VNR can be safely administered to elderly patients with MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.
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Sun, Xin, Wei Guo, Ranxin Zhang, Lu Xie, and Jie Xu. "Efficacy and safety of anlotinib combined with liposomal doxorubicin in first-line treatment of advanced soft-tissue sarcoma." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e23530-e23530. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e23530.
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e23530 Background: Anthracycline-based chemotherapy is the main first-line treatment option for advanced soft-tissue sarcoma (STS). Anlotinib has been approved for the treatment of STS by the Chinese agency. This study was performed to evaluate the efficacy and safety of Anlotinib combined with liposomal doxorubicin in first-line treatment of patients with advanced STS. Methods: This is a single-center, retrospective study. Eligible patients were those ≥14 years old, ECOG performance state of 0-1, with histologically confirmed locally advanced, unresectable or metastatic STS, previously untreated, with measurable disease by RECIST v1.1. All patients received Anlotinib (12mg once daily, 2 weeks on and 1 week off) and liposomal doxorubicin (40-50 mg/m2, IV, D1, every 3 weeks) until disease progression or unacceptable adverse events. The primary endpoint was progression-free survival (PFS). Disease control rate (DCR), objective response rate (ORR), and side effects were also calculated. Results: Between April 2019 and December 2020, 8 patients were evaluated, including 2 undifferentiated pleomorphic sarcoma, 1 liposarcoma, 4 fibrosarcomas, and 1 synovial sarcoma. The median age was 42 years. 2 patients (25%) achieved a confirmed partial response (PR) and 3(37.5%) had stable disease (SD). The ORR and DCR were 25% and 62.5% respectively. The median PFS was 11.3 months, and the PFS rate at 4 months was 50%. Treatment-related adverse events included hand-foot syndrome (3/8, 37.5%), pneumothorax (1/8, 12.5%), oral mucositis (2/8, 25%), epistaxis (2/8, 25%), hypertension (2/8, 25%), arrhythmias (1/8, 12.5%), and pharyngeal pain (1/8, 12.5%). Three patients experienced grade 3 or 4 adverse events, 2 hand-foot syndrome (2/8, 25%) and 1 pneumothorax (1/8, 12.5%). Conclusions: This study suggested that the combination of Anlotinib and liposomal doxorubicin might have anti-tumor activity and acceptable toxicity in first-line treatment of patients with advanced STS.
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Zhang, Changgong, Sheng Yang, Jianhua Chen, Huijuan Wu, Jun Wang, Yingping Li, Liying Gao, et al. "Penpulimab plus anlotinib as second-line treatment for the small cell lung cancer after failure of platinum-based systemic chemotherapy." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 8568. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8568.
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8568 Background: Combined therapy of an immune checkpoint inhibitor with a targeted anti-angiogenic agent had been proved to be effective for lung cancer. Penpulimab (AK105) was engineered to eliminate FcγR binding and antibody-dependent cell-mediated cytotoxicity (ADCC)/ antibody-dependent celluar phagocytosis (ADCP) completely, where ADCC/ADCP effects could induce T-cell apoptosis and clearance and therefore compromise anti-tumor activity. Penpulimab demonstrated a slower programmed death-1(PD-1) antigen binding off-rate, which resulted in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1. These structural differentiations enhance the anti-tumor activity of penpulimab and improve its safety. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Anlotinib has been approved by National Medical Products Administration as the treatment for small cell lung cancer (SCLC) patients, who had progressed/relapsed on or after at least two regimens of chemotherapy. Here we report the results of one cohort which received penpulimab plus anlotinib in a Phase II study. Methods: In Cohort 4 of an open-label, multi-center, multi-cohort Phase II study evaluating the efficacy and safety of penpulimab plus anlotinib in pts with advanced head, neck or chest tumors(NCT04203719), the SCLC patients, who failed to platinum-based systemic chemotherapy treatment, received penpulimab (200 mg IV Q3W) and anlotinib (12/10 mg PO 2 weeks on/1 week off). Primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival. Results: 20 patients (median age was 61 [range:37–75] years old, Eastern Cooperative Oncology Group performance status 0/1 [5%/95%], male/female [65%/35%]) were enrolled and received combination therapy (17 received 12 mg anlotinib, 3 received 10 mg anlotinib; and all received 200 mg penpulimab). At data cut-off (Jan 25, 2021), the confirmed ORR was 50.0% (10/20, 1 complete response and 9 partial response) and DCR was 75.0% (15/20). 9 PFS events (45%) had occurred, and the median PFS was 4.7 months (95% CI: 3.6-not reached). Grade 3 treatment-related adverse events (TRAEs) occurred in 30% (6/20, 2 hypertension, 1 hypertriglyceridaemia, 1 gamma-glutamyltransferase increased, 1 palmar-plantar erythrodysaesthesia syndrome and 1 hyponatraemia) of patients, No Grade 4 or 5 TRAEs had occurred. Conclusions: Penpulimab plus anlotinib showed favorable antitumor activity and an acceptable safety profile in SCLC patients who failed to platinum-based systemic chemotherapy. This new combination therapy warrants further evaluation for the treatment of SCLC. Clinical trial information: NCT04203719.
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Hanbali, Amr, Ira Wollner, Klodiana Neme, and Cynthia Ulreich. "Hypersensitivity Reaction of Gemtuzumab Ozogamicin (Mylotarg™) Associated with Platelet Transfusion: Two Case Reports." Blood 108, no. 11 (November 16, 2006): 4549. http://dx.doi.org/10.1182/blood.v108.11.4549.4549.
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Abstract Introduction Gemtuzumab ozogamicin (Mylotarg™) is a monoclonal antibody developed for the treatment of myeloid leukemias. Mylotarg is composed of a recombinant humanized IgG4 kappa antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin. It binds specifically to the CD33 antigen, which is expressed on the surface of leukemic myeloblasts and immature normal cells of myelomonocytic lineage. It is approved for the treatment of CD33 positive AML in first relapse in patients >= 60 years of age and are not considered candidates for cytotoxic chemotherapy. Hypersensitivity reactions, including anaphylactoid reactions, anaphylactic shock, dyspnea, and severe hypotension, have been reported during clinical use of gemtuzumab ozogamicin. Infrequently, hypersensitivity reactions have been fatal. It is unknown if the risk of hypersensitivity reaction increases with administration of blood products in the same day of Mylotarg infusion. We are reporting 2 cases of severe hypersensitivity reaction to Mylotarg on 2 patients who received platelete transfusion in the same day. Case reports: Case number 1: A 75 year old male diagosed with AML with normal cytogenetics in April 2005. Relapse was noted in March 2006. He was admitted for Mylotarg infusion at a dose of 9mg/m2 which was started at 11:00 a.m. after receiving the appropriate premedications and finished at 1:00 p.m. without any signs of distress or reaction. He received 6 units of platelets at 6:40 p.m. At 1:00 a.m. the next morning he went into severe respiratory distress and died shortly after that in the ICU. Case number 2: A 68 y/o male with the history of NHL in 1991, received CHOP chemotherapy in 1991 and 1992, now has secondary AML (diagnosed in October 2005 and underwent chemo in November 2005, and relapsed after induction and consolidation. He was admitted for Mylotarg infusion. Initially he received 6 units of platelets at 8:30a.m. Mylotarg was started at 10:15a.m. and finished at 12:10p.m.No signs of distress or reaction post infusion. At 2:30 p.m. the patient started having chills, rigors with fever, tachycardia, hypertension and hypoxia (pO2 86%). The patient was treated with Solu-medrol, Benadryl, Tylenol and Demerol. The reaction ceased with no further adverse events Conclusion:Mylotarg is known to cause hypersensitivity reaction, but it is unknown if the risk of this reaction increases with blood products transfusion around the time of Mylotarg transfusion. We are reporting these 2 cases to draw attention to this serious observation.
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Rha, Sun Young, Chang Gon Kim, Minkyu Jung, Hyo Song Kim, Choong-kun Lee, Hei-Cheul Jeung, Dong-Hoe Koo, et al. "Multicenter phase Ib/II study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (HER-RAM study)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4063. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4063.
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4063 Background: We evaluated the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel (TRP) as a second line treatment in human epidermal growth factor receptor 2 (HER-2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer progressed from trastuzumab containing chemotherapy. Methods: Patients with HER-2-positive advanced G/GEJ cancer who progressed after first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Trastuzumab (Herzuma[CT-P6], Celltrion Inc.) 4mg/kg on day 1 followed by 2mg/kg on days 8, 15, and 22, ramucirumab 8mg/kg on days 1 and 15, and paclitaxel (dose level 1: 80mg/m2, dose level -1: 70 mg/m2) on days 1, 8, and 15 of a 28-day cycle was tested. After safety analysis of lead-in safety cohort (phase 1b), phase 2 part was conducted to evaluate the primary endpoint of progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: At the phase 1b part, as there was no dose limiting toxicity in 3 patients at the dose level 1, dose level 1 with full dose combination was determined as recommended phase 2 dose. At the time of data lock on Jan. 31, 2021, 45 patients among enrolled 50 patients were evaluable for response and safety including 3 patients from phase 1b part. Median age was 59 years old (range 30-82) and most patients were male (37/45). At baseline, 33 patients had tumors with HER-2 3+ by immunohistochemistry (IHC) and 12 had those with HER-2 2+ by IHC with ERBB2 amplification by in situ hybridization. With median follow-up duration of 11.6 months, median PFS and OS were 7.2 months (95% confidence interval [CI]: 6.0-8.5 months) and 13.6 months (95% CI: 10.3-16.9 months), respectively. ORR was 55.6% (25/45, complete response = 1, partial response = 24) and DCR was 95.6% (43/45), respectively. Most common hematologic adverse event (AE) was neutropenia (all grade: 64.4%, grade 3/4: 51.1%) with 1 case of febrile neutropenia (2.2%). Most common non-hematologic AE was peripheral sensory neuropathy (all grade: 33.3%, grade 3: 2.2%). Gastrointestinal (GI) bleeding occurred in 4 patients (grade 3 upper GI bleeding: 6.7%, grade 1 lower GI bleeding: 2.2%), whereas GI perforation was not observed. Hypertension occurred in 3 patients (all grade: 6.7%, grade 3: 4.4%). No new or unexpected AEs resulting in treatment cessation were observed with this combination regimen. Conclusions: The continuous use of trastuzumab beyond progression in combination with ramucirumab and paclitaxel showed promising activity and manageable safety profile in HER2 positive G/GEJ cancer patients who progressed after trastuzumab containing chemotherapy. Updated outcomes for ongoing patients will be presented.
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Smith, D., M. Rouyer, P. Noize, R. Lassalle, O. Bernard, F. Burki, P. Guichard, A. Ravaud, N. Moore, and A. Fourrier-Ráglat. "Effectiveness and safety in very elderly patients treated by bevacizumab (BV) plus chemotherapy in first-line therapy of metastatic colorectal cancer: Results of ETNA, a French cohort study." Journal of Clinical Oncology 29, no. 4_suppl (February 1, 2011): 555. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.555.
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555 Background: In view of the ageing population, oncogeriatrics has become a priority for public health. Elderly cancer patients are often excluded from clinical trials and there is no therapeutic standard for their care management. Cohort studies have been conducted in US and Europe but not in France. The ETNA study aimed to describe BV use and survival outcomes in real-life practice. Here, the population aged >75 years was compared to that aged >75. Methods: ETNA is a cohort study conducted in 28 French centers that included 411 patients initiating BV between Jan 2006 and Dec 2007, with 24 month follow-up. Results: Fifty-one patients (12.4%) of the cohort were over 75 years old: mean age 78.3 years (vs 61.9 years for the rest of the cohort), male 66.7% (vs 56.1%), ECOG≥2 17.6% (vs 10.8%). BV was combined with FOLFIRI/XELIRI in 88.2% of patients aged >75 years (vs 87.5%) and FOLFOX/XELOX in 11.8% (vs 12.2%). Median duration of BV treatment was 5.6 months (m) (vs 5.5 m), and median duration of the 1st-line was 10.3 m (vs 9.8 m). More patients >75 years had treatment-free intervals (39.2% vs 28.6%), and 13.7% had a maintenance therapy (vs 12.8%). Curative surgery performed in 15.7% of patients (vs. 20.6%). Among the 43 patients who discontinued the 1st-line, only 9.3% discontinued BV prematurely (vs 18.2%). The incidence of any grade-3/4 adverse event was 43.1% (vs 41.7%). In-line with the known safety profile of BV (any grade), hypertension was observed in 21.6% (vs 18.9%), proteinuria 23.5% (vs 27.2%), there were no GI perforations (vs 0.3%), thrombotic events 5.9% (vs 7.8%), and grade 3/4 arterial thrombotic events 2.0% (vs 0.6%). The 1-year OS rate was 78.0%, 95%CI [63.9-87.2] (vs 80.5%, 95%CI [76.0-84.2]) and the median OS was not reached for both groups. The median PFS was 10.6 m, 95%CI [9.0-12.8] (vs 9.9 m, 95%CI [9.3-11.1]). Conclusions: Effectiveness and safety of BV plus chemotherapy in elderly patients were similar to those of the rest of the ETNA cohort. Estimations of survival outcomes (1-year OS rate, median OS and PFS) were also comparable to those found in elderly patients (75-80 years) from the BRITE cohort (72.0%, 20.3 m and 10.0 m, respectively). No significant financial relationships to disclose.
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Shah, Neil, Adam S. Vesole, Michele L. Donato, David S. Siegel, Joshua R. Richter, Noa Biran, Alan P. Skarbnik, Robert Korngold, Scott D. Rowley, and David H. Vesole. "Successful Renal Transplant Tolerance Following a Haplo-Identical Allogenic Hematopoietic Stem Cell Transplant - a Case Report and Review of Literature." Blood 128, no. 22 (December 2, 2016): 5879. http://dx.doi.org/10.1182/blood.v128.22.5879.5879.
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Abstract Background: Immune tolerance in solid organ transplantation is a continuing challenge because of the risks of acute and chronic rejection and severe adverse effects of extended exposure to immunosuppressive drugs (IsD). Therefore, the goal of transplant tolerance is to prevent both acute and chronic rejection without use of prolonged IsD. Owen [Science 1945] and Billingham [Nature 1953] demonstrated solid organ transplant tolerance by inducing stable donor:host chimerism with infusion of hematopoietic stem cells (HSCT). Subsequently, various animal studies and clinical trials demonstrated the ability ,of HSCT to induce solid organ transplant tolerance. Herein we present a case of an haplo-identical (HaploTx) HSC for the treatment of multiple myeloma (MM) followed thereafter by a renal transplant from the same donor. We discuss this case and results reported in the literature. Case Report: A 25-year-old male presented to the ER with complaints of fatigue, nausea, and intermittent vomiting for six months. Ultimately, he was diagnosed with kappa light chain multiple myeloma, International Staging System 3, with light chain cast nephropathy on renal biopsy (Table I). He initiated hemodialysis for worsening renal function and uncontrolled hypertension. He began chemotherapy with bortezomib, lenalidomide and dexamethasone (VRd). He responded well to chemotherapy achieving a partial remission. His free kappa light chains decreased from 2570 mg/L to 63 mg/L after 3 cycles of VRd. Considering his age, response to chemotherapy, and end stage renal disease requiring hemodialysis, the patient was offered an allogenic HSCT to be followed 1 year thereafter by a renal transplant from the same donor. Since he did not have any matched sibling donors, he underwent an HaploTx from his father after a conditioning regimen with fludarabine, cyclophosphamide and total body irradiation followed by infusion of bone marrow cells. The post-transplant IsD consisted of tacrolimus, mycophenolate mofetil and high dose cyclophosphamide (days 3 and 4). He achieved complete chimerism on d + 28 and maintained one-year post transplant. He did not develop acute GVHD but experienced limited chronic GVHD (eyes and mouth) 14-18 weeks after HSCT for which he was started on low dose prednisone and topical steroids. One year after HSCT he received renal allograft from his father. He continued to take tacrolimus post-transplant, which was tapered off by nine months. Two years following his renal transplant, his serum creatinine is 1.19mg/dl and his MM remains in complete remission (Figure I). Conclusion: Stem-cell-based therapies used in order to induce durable transplant tolerance are currently under development. Data from early trials suggest successful and durable IsD tapering in patients with combined kidney and HSCT associated with prolonged graft survival. Further, comorbidities associated with allografts have been decreased including hypertension, diabetes, and hyperlipidemia. Data from other case centers also report successful and durable IsD tapering in patients with combined kidney and HSCT associated with prolonged graft survival. However, patients with combined kidney and HSCT did develop more AKI post-transplant. Other concerns related to combined transplant are sudden death, GVHD and secondary malignancy. Ongoing clinical trials are being conducted to induce transplant tolerance to achieve either mixed chimerism and full chimerism. Results from the early clinical trials look promising, but more data is needed to assess long-term safety and efficacy. Disclosures Siegel: Amgen: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Merck: Honoraria. Richter:Takeda: Consultancy, Speakers Bureau; Jannsen: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Biran:Novartis: Speakers Bureau; Celgene: Speakers Bureau; Takeda: Speakers Bureau; Amgen: Speakers Bureau. Skarbnik:Abbvie: Consultancy; Seattle Genetics: Speakers Bureau; Gilead Sciences: Speakers Bureau; Genentech: Speakers Bureau; Pharmacyclics: Consultancy. Vesole:Celgene: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Speakers Bureau.
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Dominguez, Ligia J., Nicola Veronese, and Mario Barbagallo. "Magnesium and Hypertension in Old Age." Nutrients 13, no. 1 (December 31, 2020): 139. http://dx.doi.org/10.3390/nu13010139.
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Hypertension is a complex condition in which various actors and mechanisms combine, resulting in cardiovascular and cerebrovascular complications that today represent the most frequent causes of mortality, morbidity, disability, and health expenses worldwide. In the last decades, there has been an exceptional amount of experimental, epidemiological, and clinical studies confirming a close relationship between magnesium deficit and high blood pressure. Multiple mechanisms may help to explain the bulk of evidence supporting a protective effect of magnesium against hypertension and its complications. Hypertension increases sharply with advancing age, hence older persons are those most affected by its negative consequences. They are also more frequently at risk of magnesium deficiency by multiple mechanisms, which may, at least in part, explain the higher frequency of hypertension and its long-term complications. The evidence for a favorable effect of magnesium on hypertension risk emphasizes the importance of broadly encouraging the intake of foods such as vegetables, nuts, whole cereals and legumes, optimal dietary sources of magnesium, avoiding processed food, which are very poor in magnesium and other fundamental nutrients, in order to prevent hypertension. In some cases, when diet is not enough to maintain an adequate magnesium status, magnesium supplementation may be of benefit and has been shown to be well tolerated.
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McDonald, Laura, Peter McCarthy, Mohammad Khan, Patrick Hogan, Eileen C. Kelleher, Philip Murphy, John Quinn, et al. "Should Myelodysplastic Syndromes in Very Old Patients be More Actively Managed? Clinical Characteristics, Management and Outcomes for Patients 85 Years and Older." Blood 132, Supplement 1 (November 29, 2018): 5515. http://dx.doi.org/10.1182/blood-2018-99-113290.
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Abstract Introduction Myelodysplastic Syndrome (MDS) is classically a disease of older people, with median age at presentation of 70-75 years. The incidence of MDS is estimated at 5-13/100,000/year, but rises to >20/100,000/year in older populations. An increase in diagnosis over the last decades is in part due to improved recognition of MDS, but likely also to an increase in the ageing population. There is very little data on the clinical course, management and outcomes for very old patients (≥85 years of age) with MDS. Patients and Methods: This was a retrospective, multicentre analysis of 84 patients with MDS or Chronic Myelomonocytic Leukemia (CMML) aged ≥85 years at diagnosis from 6 centres in Ireland. Results: We identified 84 patients aged ≥85 years at time of diagnosis of MDS (n= 70) or CMML (n=14), including 47 men (56%) and 37 women (44%). Median age at diagnosis was 87 years (range 85-98). Most patients (93%) were anemic at presentation, including 45/47 men (96%) and 33/37 women (89%). Median hemoglobin (Hb) was 9.5 g/dl (range 5.9 -13.8). Median neutrophil count was 2.4 x109/L (range 0-72). Forty-four patients had thrombocytopenia (median platelet count 144 x 109/L (range 18-624)). Data regarding co-morbidities were available for 75 patients: 69% had hypertension, 36% ischemic heart disease, 39% atrial fibrillation, 31% heart failure, 19% diabetes and 39% renal dysfunction. Ferritin was elevated in 18 (32%) of 57 patients tested. 2006 WHO subgroups were reported for 81 patients: RCMD (32; 40%), CMML (14; 17%), RA (10; 12%), RAEB-1 (10; 12%), RAEB-2 (7; 9%), RARS (2; 3%), t-MDS (2; 3%), Hypoplastic MDS (1; 1%) and 5q- Syndrome (1; 1%). Cytogenetic analysis was performed in 49 patients (58%); results were available for 39 (46%). No patient had molecular studies for MDS-associated mutations or p53 deletions/mutations. Karyotype was normal in 23 patients (59% of those with results available), deletion Y in 5 (13%), Trisomy 8 in 5 (13%), complex in 3 (7.7%), 5q- in 2 (5.2%), and monosomy 7 in 1 (2.5%). Risk stratification by IPSS-R was available for only 37/84 patients, primarily due to lack of cytogenetic testing. Data were available regarding treatment strategies for 81 patients. Thirty-five (43%) received supportive care only. Forty-five patients (57%) were transfused; 29 (34%) became transfusion-dependent during the course of their disease. Of these, only 14 (48%) received erythropoietin (EPO). Of 50 patients with significant anemia likely to cause symptoms (Hb < 10g/dl), only 21 (42%) received EPO. Five patients (6%) received azacitidine (1-18 cycles; median 5), 7 (8%) received G-CSF; none received lenalidomide or iron chelation. Median survival for all patients was 17 months (range 0-147), 16 months for men (range 0-70), and 27 months for women (range 1-147). In 35 patients who had IPSS-R data available, median survival was 49 months for Very Good, 30 months for Good and 13 months for Intermediate category patients. For 4 patients in the Poor and Very Poor categories median survival was 1, 5, 7 and 28 months. Median survival for patients with RA was 28 months (n=10), RCMD 25 months (n=29), CMML 13 months (n= 14), RAEB-1 10 months (n=10) and RAEB-2 19 months (n=7). Six patients (including 3 with RAEB-1, 1 with CMML and 1 with t-MDS) developed Acute Myeloid Leukaemia (7%) at a median of 4.5 months from diagnosis. Median survival for these patients was 9.5 months. Of 84 patients, 60 have died. The main causes of death included marrow failure, sepsis, cardiac events, other malignancies and gastrointestinal bleeding. Conclusions Anemia is the commonest presenting feature of MDS in the very old, and may be the sole cytopenia. Unexplained anemia in the very old should trigger suspicion of underlying MDS, especially if associated with a high MCV. In many patients over 85 years cytogenetic analysis is not performed, precluding accurate prognostic evaluation. MDS in these very old patients is not often actively managed with pharmacological intervention or chemotherapy. Up to 50% of transfusion-dependent patients do not receive erythropoeitin. Azacitidine and lenalidomide are infrequently used. Co-morbidities (especially cardiac and renal disorders) are very common. Survival can be prolonged, especially in patients with low-risk disease. With an ageing population, management of very elderly patients with MDS is becoming more challenging and a more proactive approach should be considered. Figure. Figure. Disclosures Quinn: Janssen: Honoraria.
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Wang, Rui, Anthony Francis Yu, Richard Steingart, Sujata Patil, Jose Baselga, Larry Norton, Cliff Hudis, and Chau T. Dang. "Longer follow-up on cardiac safety and distant disease free survival of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab in patients with early-stage HER2-positive breast cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 540. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.540.
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540 Background: We previously reported the cardiac safety results and distant disease-free survival (DDFS) on a phase 2 trial of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) in patients with early stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The incidence of congestive heart failure (CHF) was 1.4% both at a median follow-up of 2 and 7 years. Here, we report updated CHF and DDFS rates with longer follow-up. Methods: Patients were enrolled with HER2 overexpressed (immunohistochemistry 3+) or amplified (fluorescent in situ hybridization ratio > 2.0) disease, regardless of size or nodal status, and baseline left ventricular ejection fraction (LVEF) of > 55%. Patients (pts) received dd AC (60/600 mg/m2) q 2 weeks (w) x 4 →T (175 mg/m2) q 2 w x 4 with H (loading dose 4 mg/kg → 2 mg/kg q w during T → 6 mg/kg q 3 w for rest of 1 year); pegfilgrastim was administered after each chemotherapy cycle. LVEF monitoring with multigated acquisition scan occurred at baseline, months 2 (after AC), 6, 9, and 18 (after therapy completion). Results: From January 2005 to November 2005, 70 pts were enrolled; 2 (3%) and 68 (97%) were treated in neoadjuvant and adjuvant settings, respectively. In 68 pts treated in adjuvant setting, 40 (60%) and 27 (40%) had node-positive and node-negative disease, respectively. The median age was 49 years old (range 27-72); 55 (79%) had hormone-receptor positive disease, 11 (16%) had hypertension, and 21 (30%) had left sided radiation. The median baseline LVEF was 68% [range, 55%-81%]). With a median follow-up of 10.9 yrs, there was no additional CHF event. Therefore, the cumulative incidence of CHF remains to be 1.4% (95% confidence interval [95% CI], 1.36%- 7.7%). The 9 and 10 year DDFS rates were 89% (95% CI, 78%-94%) and 87% (95% CI 75%-93%), respectively. Conclusions: Longer follow-up of this study has demonstrated that ddAC →TH is associated with a low risk of CHF and promising DDFS in patients with early-stage HER2-positive breast cancer.
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Lee, Jung-min, Richard G. Moore, Sharad A. Ghamande, Min S. Park, John Paul Diaz, Julia A. Chapman, James Erasmus Kendrick, et al. "Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 6056. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.6056.
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6056 Background: A Phase I trial (NCT01116648) of cediranib (cedi) in combination with olaparib (ola) (cedi + ola) demonstrated an overall response rate of 44% in patients (pts) with recurrent ovarian cancer (OC), including pts without a deleterious or suspected deleterious gBRCAm (non-gBRCAm; Liu et al. Eur J Cancer 2013). The subsequent Phase II trial (NCT01116648) showed significant improvement in progression-free survival (PFS) with cedi + ola versus ola monotherapy in recurrent platinum-sensitive OC pts, notably in non-gBRCAm pts (Liu et al. Lancet Oncol 2014). We report data from the Phase IIb, single-arm, open-label CONCERTO study investigating cedi + ola in non-gBRCAm pts with recurrent platinum-resistant OC who had received ≥3 previous lines of therapy for advanced OC (NCT02889900). Methods: Pts with disease progression <6 months from the last receipt of platinum-based chemotherapy received cedi tablets (30 mg once daily) plus ola tablets (200 mg twice daily) until progression or unacceptable toxicity. gBRCAm pts were ineligible. Primary endpoint: objective response rate (ORR) by independent central review (ICR; RECIST 1.1). Key secondary endpoints: PFS and safety. Results: 60 pts from the USA were included (median age: 64.5 years; median number of previous systemic treatment regimens: 4 [range: 2–9]; previous bevacizumab: 53). All pts had high-grade OC (90% serous; 3.3% clear cell; 3.3% endometrioid; 3.3% other). 7% of pts had tumor BRCA2 (confirmed somatic) mutations, 80% of pts had no tumor BRCA mutation (non-tBRCAm) and 13% of pts were not evaluable for tBRCAm. Five (8%) pts who were non-tBRCAm carried somatic homologous recombination repair gene mutations (FoundationOne Clinical Trial Assay, Foundation Medicine, Inc). The Table shows results of key endpoints. Most common grade ≥3 adverse events (AEs) that occurred in pts were hypertension (30%), fatigue (22%) and diarrhea (13%). 37% of pts reported serious AEs, of which nausea (7%) was most common. Dose interruptions, reductions and discontinuations were caused by AEs in 55%, 18% and 18% of pts, respectively, who received cedi + ola. Conclusions: Cedi + ola showed evidence of antitumor activity in heavily pretreated non-gBRCAm pts with recurrent platinum-resistant OC. Toxicity was manageable with dose modifications. Clinical trial information: NCT02889900. [Table: see text]
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Chen, Yi, Lan Zhang, Ningling Ge, Yanhong Wang, and Zhenggang Ren. "Clinical effect of sequential therapy of LEN combination with anti-PD1 antibody in uHCC patients who progressed on LEN treatment: A real-world data in China." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e16654-e16654. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16654.
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e16654 Background: Lenvatinib (LEN) has been used in clinical practice because of its high response rate since administrated in China. However, no recommendation is available as second-line agents after LEN treatment. The combination therapy of anti-programmed death-1(PD1) antibodies with LEN have demonstrated promising clinical efficacy in advanced HCC. Some patients were used this combination treatment after progressed on LEN in real world settings in China. Preclinical studies also showed the immune-moderate effects of LEN. This study was retrospectively analyzed the efficacy and safety of 26 unresectable HCC patients treated with LEN and anti-PD1 antibody after progressed on LEN. Methods: Unresectable HCC (uHCC) patients who treated with the combination of LEN with anti-PD1 antibody after progressed on LEN were enrolled. Patients who combine other loco-treatment and systemic therapy during the LEN combination with PD-1 antibody treatment period were excluded. The efficacy of LEN and anti-PD1 antibody was evaluated by mRECIST criteria after 2 cycles of combination treatment. AE data were recorded during the combination treatment period. Results: From October 2018 to October 2019, 26 patients were finally enrolled. As of January 10, 2020, median follow-up was 6.7±3.19 months. Median age was 56.15±11.9 years old, 80.77% (21/26) was Child-pugh(CP) A while 19.23% (5/26) was CPB7 and 88.5% (23/26) was BCLC stage C. Before combination therapy, 11 patients (42.31%) used LEN only and the other 15 patients (57.69%) were experienced sorafenib/chemotherapy before LEN. Drugs of PD1 antibodies were Keytruda and Toripalimab. The median duration of combination treatment was 6.7±3.15months. The ORR was 26.9% in total 26 cases. 2 cases of them were complete response, and the disease control rate (DCR) was 88.5% (23/26). The most common adverse events (AEs) of combination treatment were hypertension (42.31%), diarrhea (38.46%), hypothyroidism (38.46%) and anorexia (34.62%). Grade 3 or higher AEs occurred in 6 (23.08%) patients. Conclusions: This was the first real-world data of sequential therapy of LEN combination with anti-PD1 followed LEN in uHCC patients. For advanced patients who have progressed after LEN treatment, the results were promising, showing high DCR and well tolerated. 2 cases even achieve complete response. Sequential therapy may be an option for these patients. The efficacy of combination treatment needs random clinical trial to be further studied.
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Li, Peijing, Yuan yuan Yuan Chen, Shuzhen Lai, Fagui Jiang, Xiaohui Liu, Changjuan Tao, Lei Wang, et al. "A phase II study of anlotinib combined with STUPP regimen in the treatment of patients with newly diagnosed glioblastoma (GBM)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 2039. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.2039.
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2039 Background: STUPP regimen is now the standard treatment for newly diagnosed GBM, while the effectiveness is limited. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with the STUPP regimen in treating these patients. Methods: This is a phase II, multicenter, open-label, single-arm trial (NCT04119674). Thirty-three patients (17 males and 16 females) were enrolled from 8 hospitals in China between January 2019 and February 2021. Inclusion criterion included 1) newly diagnosed histologically confirmed glioblastoma (WHO grade IV), 2) 2-6 weeks (wks) after surgery with healed incision, 3) 18-70 years old, 4) KPS≥60, 5) at least one measurable lesion according to RANO criteria, 6) radiotherapy (RT), chemotherapy, immunotherapy or biotherapy naïve. All patients received 54-60 Gy radiation (1.8-2.0 Gy per fraction, five days per week) concurrently with temozolomide (TMZ, 75mg/m2, orally, QD) and anlotinib (8mg, orally, QD, d1-14/3wks). Adjuvant therapy started four weeks after RT completion, including six cycles of TMZ (150-200mg/m², orally, d1-5/4wks) and eight cycles of anlotinib (8mg, orally, QD, d1-14/3wks). Patients who completed adjuvant therapy were administrated anlotinib continuously until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of study agent. Results: The median age is 52 (range 32-69) years. Analyses included data collected through February 6, 2021. The median treatment duration was 6.5 months. The median PFS was not reached, and the median overall survival (OS) was 17.4 months [95%CI 11.6-23.2]. The 1-year PFS and OS rate was 84.0% and 100.0%, respectively. Tumor response occurred in 21 patients, 63.6% (21/33) objective response (CR/PR), and 24.2% (8/33) patients had stable disease (SD).The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than six months, was 57.6% (19/33). Hypertension (6.1%) was the most common ≥grade 3 adverse event. No treatment related death occurred in this study through the last follow-up. Overall, toxicities are mild and manageable. Conclusions: Anlotinib combined with the STUPP regimen is efficacious and well-tolerated in newly diagnosed GBM patients. Clinical trial information: NCT04119674.
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Balázs, Endre, Andrea Ruszwurm, Miklós Székely, István Wittmann, and Judit Nagy. "Old age and kidneys." Orvosi Hetilap 149, no. 17 (April 2008): 789–94. http://dx.doi.org/10.1556/oh.2008.28362.
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Age-related changes in renal morphology and function cannot be regarded physiological. The number of glomeruli falls, sclerotic glomeruli and aglomerular arterioles develop. Besides tubular atrophy interstitial fibrosis is often seen, and the age-related vascular changes strongly affect the kidneys. Renal blood flow and GFR decrease, without concomitant changes in se-creatinine. Disorders of tubular transport manifest mainly in salt- and water-excretion and lead to hyposthenuria. The pathogenesis of these age-related changes is not fully understood. Nevertheless, such changes impair the excretory functions and the pharmacokinetics of drugs. In real chronic renal failure other functions (erythropoietin production, vitamin-D, Ca and P metabolism) are also impaired. Due to more frequent occurrence of systemic diseases (diabetes, hypertension, etc.) in the elderly, real chronic renal failure is also more common, and various forms of acute renal failure develop more easily.
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Uchmanowicz, Izabella, Anna Chudiak, Beata Jankowska-Polańska, and Robbert Gobbens. "Hypertension and Frailty Syndrome in Old Age: Current Perspectives." Cardiac Failure Review 3, no. 2 (2017): 102. http://dx.doi.org/10.15420/cfr.2017:9:2.
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Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.
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FERNANDEZ, M. "P060 Hypertension as a risk factor in old age people." American Journal of Hypertension 11, no. 4 (April 1998): 225A. http://dx.doi.org/10.1016/s0895-7061(97)91544-2.
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Erdos, Benedek, Nataliya Kirichenko, Melissa Whidden, Bilgen Basgut, Mary Woods, Idan Cudykier, Rabih Tawil, Philip J. Scarpace, and Nihal Tumer. "Effect of age on high-fat diet-induced hypertension." American Journal of Physiology-Heart and Circulatory Physiology 301, no. 1 (July 2011): H164—H172. http://dx.doi.org/10.1152/ajpheart.01289.2010.
Full textAbstract:
Aging and obesity both have a significant impact on central blood pressure (BP) regulation, and previous studies indicated that changes in central redox signaling with age may affect high-fat (HF) diet-induced cardiovascular responses. Therefore, we investigated the effects of 60% HF feeding on BP regulation in young adult (5 mo) and old (26 mo) Fischer-344 × Brown-Norway rats. Radiotelemetric transmitters were implanted to measure BP, heart rate (HR), locomotor activity, and spontaneous baroreflex sensitivity. Expression and activity of NADPH oxidase and ANG II type 1 receptor were assessed in the hypothalamus and in the nucleus tractus solitarii. Old animals gained more weight on HF diet compared with young, whereas central NADPH oxidase expression and activity elevated similarly in the two age groups. After an initial hypotensive and tachycardic response during the first week of HF feeding, BP in young animals increased and became significantly elevated after 6 wk of HF feeding. In contrast, BP in old animals remained depressed. Nighttime HR and locomotor activity decreased in both young and old rats fed with HF diet, but these changes were more significant in young rats. As a result, amplitudes of circadian variation of BP, HR, and activity that were originally higher in young rats declined significantly and became similar in the two age groups. In conclusion, our experiments led to the surprising finding that HF diet has a more serious impact on cardiovascular regulation in young animals compared with old.