Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593 - A phase III trial of the Eastern Cooperative Oncology Group

Purpose: To determine the efficacy of topotecan in combination with standar d chemotherapy in previously untreated patients with extensive-stage small- cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) cond ucted a phase III trial. Patients and Methods: Eligible patients had measurable or assessable diseas e and an ECOG performance status of 0 to 2; stable brain metastases were al lowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then r andomized to observation or four cycles of topatecan (1.5 mg/m(2)/d for 5 d ays, every 3 weeks; step 2). A total of 402 eligible patients were register ed to step 1, and 223 eligible patients were registered to step 2 (observat ion, n = 111; topatecan, n = 112). Results: Complete and partial response rates to induction PE were 3% and 32 %, respectively. A 7% response rate was observed with topotecan (complete r esponse, 2%; partial response, 5%). The median survival time for all 402 el igible patients was 9.6 months. Progression-free survival (PFS) from date o f randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P < .001). However, overall surv ival from date of randomization on step 2 was not significantly different b etween the observation and topotecan arms (8.9 months v 9.3 months; P = .43 ), Grade 4 neutropenia and thrombocytapenia occurred in 50% and 3%, respect ively, of PE patients in step 1 and 60% and 13% of topotecan patients in st ep 2, Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of t opotecan patients, Grade 3/4 anemia developed in 22% of patients who receiv ed topotecan. No difference in quality of life between topatecan and observ ation was observed at any assessment time or for any of the subscale scores . Conclusion: Four cycles of PE induction therapy followed by four cycles of topatecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC, Four cycles of standard PE remains an approp riate first-line treatment for extensive-stage SCLC patients with good perf ormance status. <(c)> 2001 by American Society of Clinical Oncology.