Randomized Phase III Study of Matrix Metalloproteinase Inhibitor BMS-275291 in Combination With Paclitaxel and Carboplatin in Advanced Non-Small-Cell Lung Cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18
| Autor: | Jean-Yves Douillard, Andrea Bezjak, Dongsheng Tu, Katherine Hann, Armando Santoro, Daniel Betticher, Luis Paz-Ares, Frances A. Shepherd, Christian Peschel, Maurizio Voi, Jeffrey S. Humphrey, Andrew Arnold, Jeffrey Crawford, Natasha B. Leighl, Lesley Seymour, Jacek Jassem, Susan M. Galbraith, Alain Depierre, Ulrich Gatzemeier |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Paclitaxel Matrix metalloproteinase inhibitor Administration Oral Disease-Free Survival Carboplatin Placebos chemistry.chemical_compound Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Organic Chemicals Lung cancer Aged Performance status business.industry Imidazoles Area under the curve Cancer Middle Aged medicine.disease Matrix Metalloproteinases Surgery Clinical trial Treatment Outcome chemistry Female business |
| Zdroj: | Journal of Clinical Oncology. 23:2831-2839 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non–small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC. |
| Databáze: | OpenAIRE |
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