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Title
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Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052)
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Author
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Abstract
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| Background: This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)(1) as primary end-point. Methods: Chemotherapy-naive patients with histologically proven MPM and performance status (PS) 0/1, were treated with cisplatin 75 mg/m(2) on day 1 and bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11 every 3 weeks. The primary end-point validation utilised the landmark method. Results: Between 2007 and 2010 82 patients were entered. PFSR-18 was 53% (80% confidence intervals, CIs, 42-64%). The overall survival (OS) was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The median PFS was 5.1 months (95% CI 3.3-6.5) and the response rate was 28.4% (95% CI 18.9-39.5%). The most frequent grade 3-4 toxicities were hyponatremia (46%), hypokalaemia (17%), fatigue (12.2%), thrombocytopenia (11%), neutropenia (9.7%) and neurotoxicity (motor, sensory, other: 1.2%, 8.5%, 2.4%). There were two toxic deaths (32 and 74 days) due to acute pneumonitis and cardiac arrest. End-point validation showed that patients with no progression/progression at 18 weeks had median OS of 16.9/11.9 months, respectively. Hazard ratio was 0.46 (CI 0.32-0.67), logrank test and C-index were 0.007 and 0.60. Conclusion: The 50% PFSR-18 for CB was contained within the 80% CI for (42-64%). Therefore the null hypothesis could not be rejected. Accordingly this combination does not warrant further investigation. PFSR-18 was confirmed as a strong predictor of survival. (C) 2013 Elsevier Ltd. All rights reserved. |
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Language
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English
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Source (journal)
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European journal of cancer. - Oxford, 1990, currens
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Publication
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Oxford
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2013
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ISSN
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0959-8049
[print]
1879-0852
[online]
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DOI
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10.1016/J.EJCA.2013.05.008
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Volume/pages
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49
:13
(2013)
, p. 2815-2822
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ISI
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000322627300006
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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