Purpose: To define the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer (SCLC).
Patients and methods: Twenty-seven SCLC patients with performance status (WHO) of 0-2 and adequate renal, hepatic, and bone marrow function who had failed EP-containing front-line chemotherapy entered the study. Patients received escalated doses of topotecan (starting dose 0.5 mg/m(2)) for 5 days and epirubicin (starting dose 40 mg/m(2)) on day 8, every 28 days.
Results: All patients were assessable for toxicity and 20 for response. The MTD was topotecan 0.90 mg/m(2) and epirubicin 40 mg/m(2) with neutropenia being the most common dose-limiting event. Seventy-three courses were administered. Grade 3-4 neutropenia occurred in 22 (30%) courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thrombocytopenia in 11 (15%). Seven courses were complicated with fever and one patient died of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mild and infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses. Among 20 patients who were evaluable for response, 16 (80%) were refractory to prior treatment. One patient with refractory disease (5%) achieved a complete response of 14 weeks duration and four experienced stabilization of the disease.
Conclusions: The combination of topotecan 0.90 mg/m(2) on days 1-5, with epirubicin 40 mg/m(2) on day 8, administered every 28 days is a feasible outpatient regimen which merits further evaluation in patients with chemosensitive disease.