A dose and schedule finding study of gemcitabine and etoposide in patients with progressive non-small cell lung cancer after platinum containing chemotherapy

Background: Combination chemotherapy improves survival in patients with disseminated non-small cell lung cancer (NSCLC). Gemcitabine is active against NSCLC and etoposide has an additive effect in vitro. We describe a dose finding study for the combination of these drugs. Patients and methods: NSCLC patients progressive after chemotherapy received gemcitabine (1000 mg/m(2) days 1, 8, 15) and one of five etoposide schedules in doses ranging from 60 to 100 mg/m(2) per day administered on days 1-3 (schedules 1-2) or 8-10 (schedules 3-5). Results: 23 patients (median age 59 years) were entered. Number of patients and cycles evaluable for toxicity was 22 and 75. Non-hematological toxicity was mild. In cycle 1 leukocytopenia grade III/IV was observed in 33 and 56% of the patients treated with etoposide 60 and 80 mg/m(2) days 1-3 and in 50% treated with etoposide 60 and 80 mg/m(2) days 8-10. During cycle 1 thrombocytopenia grade III/IV was observed in 0, 33, 0 and 33% of these patients, respectively. Both patients treated at etoposide 100 mg/m(2) days 8-10 experienced febrile leukocytopenia. During cycle 1 single doses of gemcitabine were administered as planned more frequently in patients receiving etoposide 80 mg/m2 per day on days 8-10 compared to etoposide days 1-3 (83 versus 70%). Postponement of combination gemcitabine and etoposide was not necessary. The overall response rate was 21% (95% confidence interval 3-39%) with a median duration of 7.5+ months in this dose finding study. Conclusions: Combined gemcitabine-etoposide is feasible in patients with progressive NSCLC. The optimal combination was gemcitabine 1000 mg/m2 per day on days I, 8 and 15 and etoposide 80 mg/m2 per day on days 8-10 of each 28-day cycle. The response rate of 21% warrants further investigation in patients with advanced NSCLC. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.