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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 28; no. 2; pp. 157 - 162
• Main Authors: Weitz, John J, Marschke, Robert F, Sloan, Jeff A, Grill, Joseph P, Jett, James R, Knost, James A, Hatfield, Alan K, Zenk, David W, Bate, Walter W, Schaefer, Paul L
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01-05-2000
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell carcinoma; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Survival Analysis; Thrombocytopenia - chemically induced; Topotecan; Topotecan - adverse effects; Treatment Outcome; Topotecan; Cell carcinoma; Lung cancer
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/S0169-5002(99)00128-2

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.