The role of gemcitabine in the treatment of malignant mesothelioma*
Section snippets
Single-agent gemcitabine in malignant mesothelioma
Three phase II trials have evaluated the efficacy of gemcitabine as a single agent in patients with malignant mesothelioma.4, 5, 6 Gemcitabine was well tolerated at doses ranging from 1,250 to 1,500 mg/m2 in chemotherapy-naive patients. Two multicenter trials documented similarly low response rates: the European Organization for Research and Treatment of Cancer (EORTC) noted a response rate of 7% in 27 patients, while the Cancer and Leukemia Group B (CALGB) observed no responses in 17 patients.4
Gemcitabine in combination with a platinating agent in mesothelioma
The combination of gemcitabine and cisplatin is synergistic in vitro in mesothelioma cell lines3 and is active in a variety of tumor types. Four groups have investigated three different schedules of gemcitabine and cisplatin in phase II trials in mesothelioma patients; response rates have ranged from 16% to 48%.7, 8, 9 Other investigators have reported preliminary results of a phase II trial of the combination of gemcitabine and carboplatin.10 These single and multicenter trials provide level 3
Future directions for the use of gemcitabine in mesothelioma
The next generation of gemcitabine trials in malignant mesothelioma will either combine gemcitabine with other agents that have known activity in this disease, or will exploit the definite activity of the gemcitabine/platinum combination in novel contexts. Objective responses have been observed in mesothelioma patients entered on phase I trials in which gemcitabine has been combined with agents with known activity in mesothelioma, such as pemetrexed or vinorelbine.19, 20 A phase II trial of the
Conclusion
Gemcitabine has in vitro activity in mesothelioma. While it remains unclear whether gemcitabine as a single agent has any more than modest activity in this disease, the combination of gemcitabine with a platinating agent has promising activity. Phase III data to assess an impact on survival are lacking. Future approaches include combining gemcitabine with active cytotoxic or cytostatic agents, and employing active combinations as part of multimodality strategies.
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Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study
2022, ESMO OpenCitation Excerpt :In this updated analysis of the SAKK 17/16 phase II trial, lurbinectedin continues to result in prolonged OS when administered in second- or third-line therapy in a subset of patients with advanced MPM. Almost half of the patients (47%) had a median OS of ≥12 months, which compares favorably with historical trials showing OS of <9 months.15-18 Importantly, we observed a clinically meaningful subgroup of patients (19%) who experience long-term benefit from lurbinectedin and continue to be alive ≥18 months.
Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells
2014, Toxicology and Applied PharmacologyCitation Excerpt :The incidence of the disease is rising because its etiology is associated with prior exposure to asbestos, which has been worldwide used as construction material. In the majority of patients, responses to chemotherapeutic approaches are not effective and remain largely unsuccessful due to the development of chemoresistance (Kindler and van Meerbeeck, 2002; van Meerbeeck et al., 2005). However, because of hitherto low response rates, several trials are being made with new targeted agents, in the effort of improving treatment outcome.
Malignant pleural mesothelioma: Medical treatment update
2009, Clinical Lung CancerRecent advances in the treatment of malignant pleural mesothelioma
2008, Journal of Thoracic OncologyCitation Excerpt :The taxanes have yielded modest efficacy, with disease stabilization being the best response in most studies.40,41 Multiple phase II studies have demonstrated anticancer activity for gemcitabine in the treatment of MPM.39 Response rates of approximately 0 to 31% have been reported in the setting of advanced stage disease.
Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: Characterization of a novel nucleobase transport activity
2008, Biochemical PharmacologyCitation Excerpt :With either single agents or combination regimens in phase II trials, rates of tumor regression have been generally under 20% with no significant impact on median survival [49]. Although one study reported a response rate of 48% with combination cisplatin and gemcitabine [9], later studies showed lower efficacy [50]. To understand the variability of response in different clinical trials with cytotoxic nucleoside and nucleobase drugs in mesothelioma, an understanding of processes that contribute to transport of cytotoxic nucleoside and nucleobase drugs is important since variable expression of nucleoside and nucleobase antimetabolite transport activities could lead to unpredictable responses to these agents.
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Address reprint requests to Hedy Lee Kindler, MD, Assistant Professor of Medicine, University of Chicago, Section of Hematology/Oncology, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637.