A phase I clinical trial of topotecan given every 2 weeks in patients withrefractory solid tumors

Objectives: Topotecan, a potent inhibitor of the enzyme topoisomerase I, ha s shown an interesting activity against several types of solid tumors, most notably small cell lung cancer (SCLC) and ovarian cancer. We conducted a p hase I study to evaluate the dose-limiting toxicities (DLTs) and maximum to lerated dose (MTD) of topotecan given in a novel schedule of administration in patients with refractory solid tumors. Patients and Methods: Twenty-six patients with histologically confirmed diagnosis of solid tumors refractor y to all known forms of effective therapy were enrolled. The patients' medi an age was 61 years, 15 were male, and 18 had a performance status of (WHO) 0-1. Seven patients suffered from ovarian cancer, 11 from SCLC, 4 from non -SCLC, 2 from melanoma and 2 from cervical cancer. Topotecan was given for 3 consecutive days as a 30-min intravenous infusion, at doses ranging from 0.75 to 1.2 mg/m(2). Treatment was repeated every 2 weeks. Results: At dose level 5 with topotecan 1.2 mg/m(2), both study patients presented DLTs (1 patient grade 4 neutropenia and the other grade 3 fatigue), and the recomme nded doses for future phase 11 studies are topotecan 1. 1 mg/m(2) for 3 con secutive days every 2 weeks. A total of 60 treatment cycles were administer ed, with a median of 2 cycles per patient. Grade 3/4 neutropenia was observ ed in 11 (18%) cycles and 2 of them were complicated by fever requiring pat ient hospitalization. Grade 3/4 thrombocytopenia was seen in 2 (3%) cycles and grade 3 anemia in 3 (5%). Although non-hematologic toxicity was general ly mild, grade 2/3 fatigue complicated 12 (20%) cycles and grade 4 one (1.5 %) requiring treatment interruption in 4 patients. Among 18 evaluable patie nts, no objective response to treatment was observed. Conclusion: This phas e I study demonstrates that topotecan given at the dose of 1.1 mg/m(2) for 3 consecutive days every 2 weeks is a safe and tolerable regimen and possib ly permits the combination of the drug with other cytotoxic agents at clini cally relevant doses. Copyright (C) 2001 S. Karger AG, Basel.