The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma.
ABSTRACT Malignant pleural mesothelioma (MPM) is a rapidly progressive invariably lethal tumor. Treatment options remain limited and the outcome in relapsed disease is poor warranting new therapeutic options. Following our previous experience in the first-line setting, we conducted a phase 2 open-label non-comparative study to assess the safety and efficacy of weekly vinorelbine chemotherapy, each cycle consisting of 30 mg/m(2) for 6 weeks, in patients with previous exposure to chemotherapy. In 63 individuals with relapsed MPM who had not received previous vinorelbine, we observed an objective response rate of 16% and an overall survival of 9.6 months (95% confidence interval 7.3-11.8 months). The main grade III/IV toxicity observed was neutropenia and toxicity was similar to weekly vinorelbine when used in the first-line setting. Weekly vinorelbine appeared to have a reasonable response rate with an acceptable toxicity profile in the second-line treatment of MPM. Its use should be prospectively evaluated in a randomised trial in the first or second-line therapy of MPM.
SourceAvailable from: Angela Alama[Show abstract] [Hide abstract]
ABSTRACT: Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly severe, with a median survival of approximately 9-12 months and latency between exposure and diagnosis ranging from 20-50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17-22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed.Cellular and Molecular Life Sciences CMLS 02/2014; DOI:10.1007/s00018-014-1584-5 · 5.86 Impact Factor
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ABSTRACT: Background Malignant Pleural Mesothelioma (MPM) is a locally aggressive disease with a poor prognosis. After failure of first line platinum-based chemotherapy, there is no widely approved salvage regimen. New strategies for treatment are needed and phase 1 trials appear as a rationale alternative. Materials and Methods MPM patients were enrolled in 20 different phase 1 trials between March 2005 and January 2012, and their data analysed retrospectively. The primary endpoint was response rate and secondary endpoints were toxicity profile, Overall Survival (OS) and Progression Free Survival (PFS). OS and PFS were estimated using Kaplan-Meier and their association with baseline characteristics was investigated through a log-rank test. The drugs described were divided into 5 groups based on their mechanism of action. Results Forty-five patients were analyzed with a median follow up of 20.5 months. The best tumor response was as follows: 4% of patients had a RECIST partial response, 60% had stable disease, 24% had progressive disease and 11% were not evaluable. Grade ≥3 toxicities were observed in 19 (42%) patients. Median OS and PFS were estimated to 6 months (95% CI= [4.2-10.5]) and 2 months (95% CI= [1.3-2.7]), respectively. The cellular motility inhibitors group appeared as the most promising class to be developed in a phase 2 setting. Conclusion Including MPM patients in phase I trials beyond first line of treatment can result in modest clinical benefits with an acceptable toxicity profile. Several molecular pathways involved in MPM have been identified and further novel biologic therapies (are =deleted) need to be tested.Lung Cancer 08/2014; 85(2). DOI:10.1016/j.lungcan.2014.05.006 · 3.74 Impact Factor
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ABSTRACT: Objectives Pemetrexed-cisplatin is the only FDA-approved regimen for malignant pleural mesothelioma (MPM), and the impact on survival is modest. No drugs have been shown to improve survival as second-line therapy, yet vinorelbine and gemcitabine are prescribed based on the results of small phase II trials. To augment the existing limited data, we examined our institutional experience with vinorelbine and gemcitabine in patients with previously treated MPM. Materials and Methods We reviewed charts of patients with MPM treated with vinorelbine and/or gemcitabine as second- or third-line therapy between 2003 and 2010. Toxicity was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. CT scans were reviewed with a reference radiologist according to modified RECIST criteria. Results Sixty patients were identified: 33 treated with vinorelbine, 15 gemcitabine, and 12 both agents. Eight-three percent initially received pemetrexed-platinum. Toxicity was substantial: 46% experienced at least one episode of grade 3-4 toxicity. Of 56 patients evaluable radiologically, there was 1 partial response (gemcitabine) giving a response rate of 2% (95% CI 0-10%). Forty-six percent had stable disease. Median progression free survival was 1.7 months for vinorelbine and 1.6 months for gemcitabine. Median overall survival was 5.4 and 4.9 months, respectively. Conclusions Response to second- or third-line vinorelbine or gemcitabine is rare. The high rate of stable disease warrants the continued use of these agents in this setting, though the impact on survival is questionable. These data justify the choice of placebo control arms in randomized trials of novel agents in previously treated patients.Lung cancer (Amsterdam, Netherlands) 06/2014; 84(3). DOI:10.1016/j.lungcan.2014.03.006 · 3.14 Impact Factor