PHASE-I STUDY OF PACLITAXEL AND TOPOTECAN IN PATIENTS WITH ADVANCED TUMORS - A CANCER AND LEUKEMIA GROUP-B STUDY

Purpose: To define the dose-limiting toxicities (DLTs) and the recommended phase II doses of paclitaxel combined with topotecan, without and with filgrastim support. Patients and Methods: patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they herd a performance status of 0 to 1 and normal renal, hepatic, and bone marrow function, Prior treatment with taxanes or camptothecin analogs, and prior pelvic irradiation were not allowed, patients with a history of cardiac disease or on medications known to effect cardiac conduction were excluded, The dose of topotecan was fixed at 1.0 mg/m(2)/d for 5 days, The dose of paclitaxel was escalated until the maximum-tolerated dose (MTD), without and with filgrastim 5 mu g/kg subcutaneously (SC) on days 6 to 14, was reached, Paclitaxel was administered over 3 hours on day 1 before topotecan, Treatment cycles were repeated every 21 days, Results: Of 46 patients entered, 45 were assessable for toxicity and 34 for response, The principal toxicity was neutropenia Without filgrastim, the MTD of paclitaxel was 80 mg/m(2) on day 1 in combination with topotecan 1.0 mg/m(2)/d for 5 days. With filgrastim, the dose of paclitaxel wets escalated to 230 mg/m(2) in combination with the same dose of topotecan. At this dose level, one patient had hematologic DLT and a second patient developed neuromuscular DLT, Three patients had a partial response (PR): one with head and neck canter, a second with non-small cell lung cancer, and the third with colon cancer. Conclusion: We conclude that paclitaxel can be given at clinically relevant doses in combination with topotecan and filgrastim, The recommended dose for phase II studies is paclitaxel 230 mg/m(2) on day 1 and topotecan 1.0 mg/m(2)/day for 5 days with filgrastim 5 mu g/kg on days 6 to 14. (C) 1995 by American Society of Clinical Oncology.