Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer
| Autor: | Christian Peschel, Jeffrey S. Humphrey, Maurizio Tonato, Jean-Yves Douillard, Luis Paz-Ares, Maurizio Voi, Lesley Seymour, Anne Van Vreckem, Andrew Arnold, Katherine Young, Frances A. Shepherd, Dongsheng Tu, Michael Smylie, J. Ottaway, Mary Davis |
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| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Cancer Research medicine.medical_specialty Randomization Lung Neoplasms Paclitaxel medicine.medical_treatment education Administration Oral Placebo Gastroenterology Carboplatin Placebos chemistry.chemical_compound Double-Blind Method Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Humans Organic Chemicals Lung cancer Infusions Intravenous Aged Chemotherapy business.industry digestive oral and skin physiology Imidazoles Middle Aged medicine.disease Rash Matrix Metalloproteinases Surgery stomatognathic diseases Oncology chemistry Toxicity Female medicine.symptom business |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 46(3) |
| ISSN: | 0169-5002 |
| Popis: | Background: This randomized, double-blind, placebo-controlled study was designed to assess whether the addition of the matrix metalloproteinase (MMP) inhibitor BMS-275291 to combined paclitaxel and carboplatin chemotherapy had an adverse impact on expected tumor response or had significant toxicity, especially arthrotoxicity, in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Seventy-five chemotherapy-naive patients with stage IIIB–IV NSCLC were randomly assigned to BMS-275291 or placebo. All patients received paclitaxel 200 mg/m 2 as a continuous 3-hour infusion followed by carboplatin calculated using the Calvert formula for a target AUC of 6 mg/(ml min), every 21 days for a maximum of eight cycles. BMS-275291 or placebo was administered on an outpatient basis at a daily oral dosage of 1200 mg. Results: All 75 patients were evaluable for toxicity and 65 (86.7%) for response. Drug-related arthrotoxicity ≥grade 2 occurred in 12 patients (31.6%) in the BMS-275291 group (lower limit of one-sided 95% CI: 19.3) and in 11 patients (29.7%) in the placebo treatment arm. The incidence of rash was higher in patients receiving BMS-275291 (28.9% versus 18.9%). An objective response rate of 21.9% was observed in the BMS-275291 treatment arm and 36.4% in the placebo arm. Conclusion: BMS-275291 plus paclitaxel/carboplatin was well tolerated and active in advanced non-small cell lung cancer. Treatment with BMS-275291 was not limited by drug-related arthrotoxicity and tumor response was as expected. As planned, patient accrual continued to further investigate the effect of BMS-275291 on overall and progression-free survival in a phase III setting. |
| Databáze: | OpenAIRE |
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