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Статті в журналах з теми "Gold-standard chemotherapy regimens"
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Tankel, James, and Lorenzo Ferri. "New Approaches to Neoadjuvant Treatment for Locally Advanced Esophageal Cancer." Foregut: The Journal of the American Foregut Society 2, no. 2 (June 2022): 143–53. http://dx.doi.org/10.1177/26345161221108331.
Повний текст джерелаАнотація:
The treatment paradigm of esophageal carcinoma is evolving as is the appreciation that histology drives treatment decisions. For adenocarcinoma, neoadjuvant chemotherapy followed by en bloc transthoracic resection is the gold standard of care. In this setting, the addition of radiotherapy does not seem to be associated with a survival benefit. For squamous cell carcinoma, neoadjuvant chemoradiotherapy is currently the best therapeutic option. However, modern neoadjuvant chemotherapy regimens may engender better survival outcomes for these patients too. Moreover, the role of immunomodulating therapies and selective surgical approaches are yet to be fully appreciated and may influence future recommendations.
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Passardi, Alessandro, Emanuela Scarpi, Luigi Cavanna, Annalisa Fontana, Bernadette Vertogen, Silvia Ruscelli, Emiliano Tamburini, et al. "Effectiveness of bevacizumab added to gold standard chemotherapy in metastatic colorectal cancer (mCRC): Final results from the Itaca randomized clinical trial." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3517. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3517.
Повний текст джерелаАнотація:
3517 Background: Evidence from available RCTs indicates that the addition of bevacizumab (B) to chemotherapy (CT) results into an improved survival in metastatic colorectal cancer (mCRC). However, the magnitude of this effect is different across trials, with marginal benefit observed when gold standard CT regimens are used. With these premises we performed a phase III randomized clinical study to evaluate the effectiveness of gold standard mCRC first line CT + B. This study was funded by the Italian Ministry of Health. Methods: mCRC patients candidate were randomized to receive first line CT +B or first line CT alone. CT regimens included FOLFOX4 (oxaliplatin 85 mg/m2 d1, folinic acid FA 100 mg/m2 dd1,2, 5FU 400 mg/m2 iv bolus dd 1,2 plus 5FU 600 mg/m2 22-h ic dd1,2 – Q14 days) or FOLFIRI (irinotecan 180 mg/m2d1, FA and 5FU as in FOLFOX4, Q 14 days); B 5 mg/kg was administered Q 14 days. The primary end point was Progression Free Survival (PFS). Secondary endpoints included Overall Survival (OS), Response Rate (ORR) and safety. Three hundreds ten events were required to statistically differentiate PFS between groups with 80% power. Results: Between 11/2007 and 03/2012, 376 patients were randomized. Patient characteristics were well balanced between the two arms. FOLFOX4 was used in 60% of the patients and FOLFIRI in 40%. After a median follow up of 18.4 months, 313 progressions and 179 deaths were observed. No statistically significant differences in PFS, OS and ORR were observed (see table). B containg regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia. Conclusions: The addition of B to a gold standard CT for mCRCdoes not result into an improved prognosis in terms ofPFS, ORR, OS. ITACA’s results (control arm) suggest that the chemotherapeutic schedules used in some of the previously published bevacizumab trials might be suboptimal. Clinical trial information: 2007-004539-44. [Table: see text]
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Eldridge, Sandy, Liang Guo, and John Hamre. "A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models." Toxicologic Pathology 48, no. 1 (July 22, 2019): 190–201. http://dx.doi.org/10.1177/0192623319861937.
Повний текст джерелаАнотація:
Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect caused by several classes of widely used anticancer therapeutics. Chemotherapy-induced peripheral neuropathy frequently leads to dose reduction or discontinuation of chemotherapy regimens, and CIPN symptoms can persist long after completion of chemotherapy and severely diminish the quality of life of patients. Differences in the clinical presentation of CIPN by widely diverse classifications of anticancer agents have spawned multiple mechanistic hypotheses that seek to explain the pathogenesis of CIPN. Despite its clinical relevance, common occurrence, and extensive investigation, the pathophysiology of CIPN remains unclear. Furthermore, there is no unequivocal gold standard for the prevention and treatment of CIPN. Herein, we review in vivo and in vitro models of CIPN with a focus on histopathological changes and morphological features aimed at understanding the pathophysiology of CIPN and identify gaps requiring deeper exploration. An elucidation of the underlying mechanisms of CIPN is imperative to identify potential targets and approaches for prevention and treatment.
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Arjunan, Ananth, and Hema Rai. "Central Nervous System Involvement by Waldenstrom Macroglobulinemia: A Case Report of the Bing–Neel Syndrome." Case Reports in Hematology 2019 (March 14, 2019): 1–3. http://dx.doi.org/10.1155/2019/4075960.
Повний текст джерелаАнотація:
Bing–Neel syndrome (BNS) is a rare complication of Waldenstrom macroglobulinemia (WM) defined by a lymphoplasmacytic infiltration of the central nervous system (CNS). Patients present with a range of neurologic symptoms of variable severity. Diagnosis requires a low threshold of suspicion and is considered in WM patients with unexplained neurologic symptoms. It can occur in the presence of quiescent serum markers of WM. Direct CNS tissue biopsy should be pursued if feasible and remains the gold standard for diagnosis. No standard of care treatment exists, but expert guidelines suggest intravenous chemotherapy in standard dose or high-dose regimens or use of oral ibrutinib. Consideration is also made for intravenous rituximab, intrathecal therapies, and autologous stem cell transplantation. Patient factors and tolerability should drive decisions regarding treatment choice in this arena, given a lack of data for standard frontline therapy.
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Jung, Sara, Zoltan Nagy, Martin Fassnacht, Gerard Zambetti, Max Weiss, Martin Reincke, Peter Igaz, Felix Beuschlein, and Constanze Hantel. "Preclinical progress and first translational steps for a liposomal chemotherapy protocol against adrenocortical carcinoma." Endocrine-Related Cancer 23, no. 10 (October 2016): 825–37. http://dx.doi.org/10.1530/erc-16-0249.
Повний текст джерелаАнотація:
Systemic therapy of adrenocortical carcinoma (ACC) is limited by heterogeneous tumor response and adverse effects. Recently, we demonstrated anti-tumor activity of LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane), a liposomal variant of EDP-M (etoposide, doxorubicin, cisplatin, mitotane). To improve the therapeutic efficacy and off-target profiles of the clinical gold standard EDP-M, we investigated liposomal EDP-M regimens in different preclinical settings and in a small number of ACC patients with very advanced disease. Short- and long-term experiments were performed on two ACC models (SW-13 and SJ-ACC3) in vivo. We evaluated the anti-tumoral effects and off-target profiles of EDP-M, LEDP-M and a novel regimen L(l)EDP-M including liposomal etoposide. Furthermore, the role of plasma microRNA-210 as a therapeutic biomarker and first clinical data were assessed. Classical and liposomal protocols revealed anti-proliferative efficacy against SW-13 (EDP-M P < 0.01; LEDP-M: P < 0.001; L(l)EDP-M: P < 0.001 vs controls), whereas in SJ-ACC3, only EDP-M (P < 0.05 vs controls) was slightly effective. Long-term experiments in SW-13 demonstrated anti-tumor efficacy for all treatment schemes (EDP-M: P < 0.01, LEDP-M: P < 0.05, L(l)EDP-M P < 0.001 vs controls). The analysis of pre-defined criteria leading to study termination revealed significant differences for control (P < 0.0001) and EDP-M (P = 0.003) compared to L(l)EDP-M treatment. Raising its potential for therapy monitoring, we detected elevated levels of circulating microRNA-210 in SW-13 after LEDP-M treatment (P < 0.05). In contrast, no comparable effects were detectable for SJ-ACC3. However, overall histological evaluation demonstrated improved off-target profiles following liposomal regimens. The first clinical data indicate improved tolerability of liposomal EDP-M, thus confirming our results. In summary, liposomal EDP-M regimens represent promising treatment options to improve clinical treatment of ACC.
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Bila, Jelena, Mirjana Gotic, and Biljana Mihaljevic. "New concept of the treatment in elderly patients with multiple myeloma." Srpski arhiv za celokupno lekarstvo 139, suppl. 2 (2011): 110–15. http://dx.doi.org/10.2298/sarh11s2110b.
Повний текст джерелаАнотація:
The traditional concept of treatment of patients aged over 65 years with multiple myeloma is historical combination of melphalan and prednisone (MP). The introduction of novel agents, such as immunomodulatory drugs and proteasome inhibitors, has crucially changed the course and prognosis of this disease. The new gold standard of treatment in elderly patients with multiple myeloma is based on synergistic combination of standard MP chemotherapy and novel agents such as thalidomide and bortezomib, as a part of MPT and MVP regimens. Furthermore, promising results have been also obtained with MP plus new generation of immunomodulatory drug lenalidomide. In some patients aged over 65 years and in good general condition, reduced-intensity autologous stem cell transplantation can be an option with application of reduced intensity conditioning regimens and novel agents incorporated into pre-transplant induction treatment and post-transplant consolidation. Certain concern regarding treatment-related adverse events can be overcome by adequate prophylaxis, conscientious follow-up, timely dose-reduction, and application of reducedintensity MPT and MPV in patients aged over 75 years. The last therapy of choice should be individually tailored according to the clinical profile of the patient and expected toxic effects of planned treatment.
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Irino, Tomoyuki, Hiroya Takeuchi, Masanori Terashima, Toshifumi Wakai, and Yuko Kitagawa. "Gastric Cancer in Asia: Unique Features and Management." American Society of Clinical Oncology Educational Book, no. 37 (May 2017): 279–91. http://dx.doi.org/10.1200/edbk_175228.
Повний текст джерелаАнотація:
Gastric cancer (GC) poses a burden to patients across the globe as the third leading cause of cancer deaths worldwide. Incidence of GC is particularly high in Asian countries, which is attributed to the prevalence of Helicobacter pylori (H. pylori) infection and has prompted the establishment of unique treatment strategies. D2 gastrectomy, which was established in the 1950s in Japan, has served as a gold standard for locally advanced GC for over half a century. Since the beginning of the 21st century, endoscopic resection (ER) techniques and minimally invasive laparoscopic surgery have greatly changed the treatment of patients with early GC. S-1, which showed a striking survival benefit in a large randomized trial in Japan, has been used as adjuvant therapy for the last decade. Likewise, S-1–based chemotherapy regimens are currently the standard of care for the treatment of unresectable/metastatic GC in Asia. Along with the development of standardized therapy, novel techniques and new drugs have been rapidly brought into clinical practice. State-of-the-art sentinel node (SN) navigation surgery enables clinicians to perform truly minimally invasive surgery for early GC, and appropriate chemotherapy regimens are now determined by a tumor’s molecular expression. New classifications based on gene signatures are proposed and may replace conventional clinical classifications. Such highly individualized treatment has the potential to alter our clinical practice in GC in the near future. The best practice in each geographic region should be shared and integrated, resulting in the best practice without borders.
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Affronti, M. L., J. M. Day, J. E. Herndon, J. N. Rich, J. A. Quinn, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, R. E. McLendon, and H. S. Friedman. "Radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy for glioblastoma (GBM) patients." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 2068. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2068.
Повний текст джерелаАнотація:
2068 Background: GBM is the most lethal type of brain tumor with a 1 yr median survival. We hypothesized that GBM patients who receive adjuvant rotational multi-agent chemotherapy (temozolomide, CCNU, and CPT-11) have improved overall survival when compared to patients receiving single agent adjuvant regimens (carmustine, temozolomide). Methods: We conducted an IRB-approved retrospective data analysis of 80 primary GBM patients who received radiation therapy and concurrent temozolomide followed by 12 mos of adjuvant rotational multi-agent chemotherapy. All patients with the intent to treat were included in the analysis. The survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA). These data were compared to the recently published Stupp RPA analysis (JCO 2006) and the RTOG trial (radiation alone). Results: 73% were male. Mean age was 52 yrs (range 21–76 yrs); 39 % were < 50 yrs.. 82% were white. WHO performance status was: 0, 14%; 1, 62%; 2, 20%; and 3, 4%. Overall survival was 59% (95% CI: 49%, 71%) at 1 yr and 31% (23%, 43%) at 2 yrs. Median survival was 65.1 wks (49.7, 78.9) with median follow-up of 122.1 wks.. No difference in the 2-yr overall survival rate in RPA classes III-IV was detected between the Duke and Stupp regimens (p>0.4733), but 66% (33, 77) of the Duke rotational therapy GBM patients are living longer than the RTOG patients (p > 0.0086). Univariate Cox Hazard ratio of 1.27 (0.522, 3.08) did not correlate MGMT status with survival (p > 0.60). Conclusions: (1) Concurrent Temozolomide and radiation followed by rotational chemotherapy is an effective therapy compared to recent published gold standard adjuvant regimens. (2) Concurrent Temozolomide and radiation followed by rotational chemotherapy resulted in a statistically significant survival benefit compared to RTOG trial. (3) Lack of correlation between MGMT and overall survival suggests that agents whose damage is not repaired by MGMT may be an important therapeutic approach. (4) Future prospective randomized trials with concurrent Temozolomide and radiation must compare post radiation multi-modality regimens. No significant financial relationships to disclose.
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Morris, Julia M., and Curtis A. Thorne. "Abstract 3087: The identification and characterization of FOLFOX chemotherapy resistant cell lineages in colorectal cancer organoids." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3087. http://dx.doi.org/10.1158/1538-7445.am2022-3087.
Повний текст джерелаАнотація:
Abstract Resistance to chemotherapy drugs is a well-documented issue inhibiting the treatment of a wide variety of cancers. Colorectal cancer (CRC) is the third most common neoplasm worldwide and has the third highest mortality rate. However, the longtime gold-standard FOLFOX chemotherapy regimen, consisting of 5-FU and Oxaliplatin, results in only 70% survival rates in Stage 3 CRC patients, worse in Stage 4. More recent targeted therapies have marginally improved on this number, but the fact remains that CRC represents a highly heterogeneous neoplasm and resistance to standard chemotherapeutic regimens poses a significant barrier in treating this devastating disease. There is an immediate need to better understand how this resistance arises. We hypothesize that a small number of cells with high phenotypic plasticity (HPP) are able to remain dormant during the initial chemotherapy treatment then reenter the cell cycle to cause recurrence and metastasis months or even years after treatment has concluded. Patient-derived organoids (PDOs) are a recently developed ex vivo model that allows for the study and extensive characterization of such HPP cell populations that may be found in patient tumors. We are developing and expanding various PDO populations to examine them genotypically and phenotypically on the single-cell level through RNA sequencing and high throughput imaging, respectively. By identifying these HPP cell populations, we then discover drugs that prevent the development of drug-resistant subpopulations. In the long term, we use our tumor heterogeneity profile to develop models that predict the responsiveness of tumors, including their drug-resistant HPP subpopulations, to well-documented and clinically used oncology drugs, streamlining treatment and improving survival outcomes. Citation Format: Julia M. Morris, Curtis A. Thorne. The identification and characterization of FOLFOX chemotherapy resistant cell lineages in colorectal cancer organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3087.
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Bredin, Philip, Joseph J. McKendrick, Prasad Cooray, and Rachel Wong. "Small bowel adenocarcinoma treatment: A single centre experience." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 451. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.451.
Повний текст джерелаАнотація:
451 Background: Small bowel adenocarcinoma (SBA) has a high mortality. Randomised controlled trials are not feasible due to its rarity, therefore there is no gold standard treatment approach. Surgical resection for early stage disease is the only potentially curative option. Systemic therapeutic options are generally extrapolated from oesophagogastric and colorectal chemotherapy regimens. Methods: This is a retrospective review of treatment and outcomes for SBA patients who attended Eastern Health between 1st January 2010 and 30thJune 2015. Approval was obtained from the Eastern Health Human Research and Ethics Committee. Results: Thirty-six patients with SBA were identified: 16 (44%) duodenal, 12 (33%) ampullary, 6 (17%) jejunal, 2 (6%) terminal ileum, 1 not specified. Median age was 72 and 25 (69%) were male. Stage at diagnosis was as follows: Stage 1 = 4 (11%), Stage 2 = 8 (22%), Stage 3 = 9 (25%) and Stage 4 = 10 (28%). Surgery with curative intent occurred in 19 patients (Whipple’s = 13, wide local excision = 6) of whom 6 received adjuvant (predominantly fluoropyrimidine-based) chemotherapy. One patient died from post-operative complications. At last follow-up, 8 patients remained in complete remission; 11 had relapsed; 3 were lost to follow-up. Three patients had died due to disease. Median relapse-free survival in the curative-intent group was 21.4 months. Median overall survival (OS) has not been reached. Sixteen patients were initially treated with palliative intent. Ten underwent palliative surgery (bypass = 7; resection = 3). Overall, 16 patients commenced palliative chemotherapy, including 8 from the curative-intent group post-relapse. The most commonly used regimen was oxaliplatin plus fluoropyrimidine. Best responses to chemotherapy were partial response = 5 (31%) and stable disease = 4 (25%). Six patients received second-line chemotherapy. Median progression-free survival on first-line chemotherapy was 4.8 months. Median OS was 9.4 months. Conclusions: SBA has a poor prognosis. Although 56% of advanced SBA patients had disease control using chemotherapy extrapolated from other gastrointestinal malignancies, responses were not durable.
Дисертації з теми "Gold-standard chemotherapy regimens"
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Sorensen, James. "Therapeutic Efficacy of a Co-Q10 Analogue in Combating Cachexia and Mortality Induced by Gold-Standard Paediatric Chemotherapy Regimens." Thesis, 2020. https://vuir.vu.edu.au/41826/.
Повний текст джерелаАнотація:
Chemotherapy is an effective first-line treatment against cancer; however, it induces a myriad of serious sequalae, including skeletal muscle dysfunction and wasting (SMDW) and fatigue, which we hypothesise is underpinned by mitochondrial dysfunction. When chemotherapy-induced (CI) SMDW is instigated in childhood, it often endures and manifests over the lifespan resulting in exacerbated morbidity and, in some cases, mortality. Despite much research having investigated individual chemotherapeutic agents and their effect on the skeletal muscle in mice (including our own), these models failed to evaluate the potential interactions between agents in a poly-pharmaceutical regimen, or, the effects of long-term and multi-staged chemotherapy regimens like that used in hospitals world-wide. Therefore, this thesis investigated the impact that gold-standard chemotherapy regimens used to combat the three common childhood cancers: acute lymphoblastic leukaemia (ALL), non- Hodgkin’s Burkitt lymphoma (NHBL) and medulloblastoma, on the skeletal muscle system in healthy juvenile mice and monitored the effects of treatment endured over the lifespan.
After establishing pre-clinical animal models for three gold-standard chemotherapy regimens, we showed that, regardless of regimen, eight weeks of treatment to four-week-old mice induced considerable skeletal muscle dysfunction which was characterised by significant muscle weakness, fatigability and, in 2 of the 3 regimens, lean mass loss. Although the age of onset of these sequalae were variable (varying between eight-weeks and 30-weeks of life), mitochondrial dysfunction was evident, identifying a point for therapeutic intervention. As such, we investigated the efficacy of daily Idebenone treatment (a powerful antioxidant and mitochondrial Co-Q10 analogue) against mitochondrial dysfunction and thus CI-SMDW. Idebenone co-therapy greatly improved mitochondrial performance in chemotherapy- treated mice, as well as protecting against lean mass loss and improving overall strength in the more aggressive chemotherapy regimen used against NHBL. Moreover, Idebenone co- therapy was shown to completely abate chemotherapy-induced mortality in the NHBL regimen, reducing mortality from 77% to zero.
This thesis shows that childhood chemotherapy, regardless of the aggressiveness of the regimen or the classes of drugs used, induces life-long SMDW which is likely contributed to by mitochondrial dysfunction. The mitochondrial targeting therapeutic, Idebenone, shows promising potential for clinical application against the SMDW sequalae and mortality induced by some regimens, with the potential to improve childhood chemotherapy patient outcomes and survivability.