Randomized Phase III Trial of Paclitaxel, Etoposide, and Carboplatin Versus Carboplatin, Etoposide, and Vincristine in Patients With Small-Cell Lung Cancer

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Abstract
Background: Paclitaxel administered in combination with a topoisomerase-II inhibitor (such as etoposide) and carboplatin is an effective and safe first-line treatment for patients with small-cell lung cancer (SCLC). We conducted a randomized phase III multicenter trial to determine whether paclitaxel plus etoposide plus carboplatin improves the outcome of patients with primary SCLC relative to standard chemotherapy (carboplatin, etoposide, and vincristine). Methods: Between January 1998 and December 1999, 614 patients with SCLC stages I–IV were randomly assigned to the standard arm (309 patients) or the experimental arm (305 patients). Treatment courses were repeated every 21 days for a maximum of six courses. All patients were evaluated for response rate, survival, and toxicities every two courses. The primary endpoint was survival. Survival curves were estimated with the Kaplan–Meier method and compared using the log-rank test. All statistical tests were two-sided. Results: A total of 608 patients were evaluable for all endpoints (standard arm 307 patients, experimental arm 301 patients). The hazard ratio [HR] of death for patients receiving the standard treatment was statistically significantly higher than that for patients receiving the experimental treatment (HR = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P = .024). Progression-free survival was also statistically significantly shorter for patients in the standard arm relative to that of patients in the experimental arm (HR = 1.21, 95% CI = 1.03 to 1.42). There were no differences in the response rates (complete and partial combined) to the treatments (standard arm: 69.4%, 95% CI = 63.9% to 74.5%; experimental arm: 72.1%, 95% CI = 66.7% to 77.1%; difference = 2.7%, 95% CI = 4.5% to 9.9%). Rates of severe grade of anemia, leukocytopenia, neutropenia, and thrombocytopenia were lower in the experimental arm than in the standard arm. Conclusion: Patients with previously untreated SCLC who received paclitaxel, etoposide, and carboplatin showed improved overall and progression-free survival and less frequent hematologic toxicities than those who received the standard therapy.