A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer

Abstract We conducted a randomized phase II trial of two different schedules of topotecan in patients with advanced-stage non small lung cancer (NSCLC) without prior cytotoxic chemotherapy. All patients had histologic or cytologic confirmation of stage IV (M1) or III-B NSCLC. Patients were stratified by performance status, stage and weight loss. Patients were randomized to receive topotecan at intravenous doses of 1.5 mg/m 2 /day over 30 min for 5 days every 3 weeks (Arm A) or 1.3 mg/m 2 /day by continuous infusion pump over 72 h every 4 weeks (Arm B). Thirty-eight patients in Arm A and 37 patients in Arm B were deemed evaluable for response and toxicity. Six tumor responses (16%, 4 PR, 2 REGR) were observed among 38 evaluable patients in Arm A and all responses occurred in patients with adenocarcinoma. In Arm B, 3 tumor responses (8%, 2 PR, 1 REGR) occurred among 37 evaluable patients and responses occurred in patients with squamous cell carcinoma (1) and adenocarcinoma (2). Toxicities >grade 3 in both arms included leukopenia, thrombocytopenia, malaise, constipation, diarrhea, lethargy, pulmonary, vomiting, infection and myalgia. Severe (≥ grade 3) thrombocytopenia occurred in 15.8% of Arm A patients and 37.8% of Arm B patients and this difference was statistically significant ( P =0.03). The median times to progression are 101 and 63 days ( P =0.75) and the median survival times are 257 and 179 days ( P =0.83) for Arms A and B, respectively. These differences in time to progression and overall survival are not statistically significant. Topotecan has limited, single agent activity in advanced NSCLC when given as 1.5 mg/m 2 /day over 30 min for 5 days every 3 weeks. We do not intend to pursue further investigations with topotecan in patients with NSCLC.