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

Background: Combination chemotherapy improves survival in patients with dis seminated non-small cell lung cancer (NSCLC). Gemcitabine is active against NSCLC and etoposide has an additive effect in vitro. We describe a dose fi nding 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 6 0 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. Nu mber of patients and cycles evaluable for toxicity was 22 and 75. Non-hemat ological toxicity was mild. In cycle 1 leukocytopenia grade III/IV was obse rved 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. Du ring 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 d oses of gemcitabine were administered as planned more frequently in patient s receiving etoposide 80 mg/m2 per day on days 8-10 compared to etoposide d ays 1-3 (83 versus 70%). Postponement of combination gemcitabine and etopos ide was not necessary. The overall response rate was 21% (95% confidence in terval 3-39%) with a median duration of 7.5+ months in this dose finding st udy. Conclusions: Combined gemcitabine-etoposide is feasible in patients wi th progressive NSCLC. The optimal combination was gemcitabine 1000 mg/m2 pe r day on days I, 8 and 15 and etoposide 80 mg/m2 per day on days 8-10 of ea ch 28-day cycle. The response rate of 21% warrants further investigation in patients with advanced NSCLC. (C) 1999 Elsevier Science Ireland Ltd. All r ights reserved.