A dose escalation study of topotecan in combination with epirubicin in pretreated patients with small-cell lung cancer

Purpose: To define the dose-limiting toxicities (DLTs) and the maximum tole rated doses (MTDs) of topotecan in combination with epirubicin in pretreate d patients with small-cell lung cancer (SCLC). Patients and methods: Twenty -seven SCLC patients with performance status (WHO) of 0-2 and adequate rena l, hepatic, and bone marrow function who had failed EP-containing front-lin e chemotherapy entered the study. Patients received escalated doses of topo tecan (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 1.0 for response. The MTD was topotecan 0.90 mg/m(2) and e pirubicin 40 mg/m(2) with neutropenia being the most common dose-limiting e vent. Seventy-three courses were administered. Grade 3-4 neutropenia occurr ed in 22 (30%) courses, grade 3-4 anemia in 7 (10%), and grade 3-4 thromboc ytopenia in 11 (15%). Seven courses were complicated with fever and one pat ient died of neutropenic sepsis. Grade 3-4 non-hematologic toxicity was mil d and infrequent with only grade 2-3 asthenia occurring in 16 (22%) courses . Among 220 patients who were evaluable for response, 16 (80%) were refract ory 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 d ays 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. (C) 2001 Elsevier Science Ireland Ltd. All rig hts reserved.