Cisplatin–etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC): A multicenter phase II study

Abstract

Purpose: In order to investigate the feasibility of a potentially non-cross resistant drug regimen, we alternated cycles of cisplatin–etoposide with topotecan as front-line treatment in patients with extensive stage small cell lung cancer (SCLC). Patients and Methods: Thirty-six previously untreated patients with extensive stage SCLC received cisplatin 75 mg/m 2 IV on day 1 and etoposide 100 mg/m 2 IV on days 1–3 on cycles one, three, five and seven and topotecan 1.5 mg/m 2 IV on days 1–5 on cycles two, four, six and eight. Cycles were repeated every 21 days. Patients' median age was 60 years and performance status (WHO) was 0 for 13, 1 for 20 and 2 for three patients. All patients were evaluable for response and toxicity. Results: Five (14%) patients achieved a complete response and 18 (50%) a partial response for an overall response rate of 64% (95% confidence interval: 48.2–79.6%). After a median follow up of 10 months, the median duration of response was 5.5 months, the time to tumor progression 8 months and the probability of 1-year survival 48.9%. A total of 126 cycles of cisplatin–etoposide and 117 cycles of topotecan were administered with a median number of 4 cycles/patient for each regimen. There were no toxic deaths. Treatment delays due to toxicity occurred in 13 (10%) cycles after cisplatin–etoposide and 16 (14%) cycles after topotecan while doses were reduced in seven (6%) and five (4%) cycles, respectively. Grade 3–4 neutropenia, thrombocytopenia and febrile neutropenia complicated 13, 1 and 3% of cisplatin–etoposide cycles and 28, 6 and 1% of topotecan, respectively. Non-hematologic toxicity was mild. The delivered dose intensity was 96% for cisplatin and etoposide and 98% for topotecan. Conclusions: The alternating administration of cisplatin–etoposide and topotecan is a feasible, active and well-tolerated regimen in patients with extensive stage SCLC.