Phase I trial of paclitaxel, carboplatin, and topotecan with or without filgrastim (granulocyte-colony stimulating factor) in the treatment of patients with advanced, refractory cancer

BACKGROUND. Topotecan is a new antineoplastic agent with a broad spectrum o f activity. The purpose of this Phase I trial was to define the maximum tol erated dose of topotecan when added to the widely used combination of pacli taxel and carboplatin, METHODS. Patients with advanced cancer that was refractory or resistant to standard treatments were treated with paclitaxel, carboplatin, and topoteca n; doses were escalated in sequential cohorts of patients. After definition of the maximum tolerated dose without cytokines, granulocyte-colony stimul ating factor (G-CSF) was added and further dose escalation was attempted. RESULTS. The maximum tolerated doses were: paclitaxel, 135 mg/m(2), as a 1- hour intravenous (i.v.) infusion on Day 1; carboplatin, area under the curv e 5.0, on Day 1; and topotecan, 0.75 mg/m(2), i.v. on Days 1, 2, and 3; the regimen was repeated every 21 days. Myelosuppression, particularly thrombo cytopenia, was the dose-limiting toxicity with this three-drug combination. Nonhematologic toxicity was uncommon. The addition of G-CSF did not allow substantial dose escalation because thrombocytopenia was uneffected by this agent. Eleven of 25 patients had major responses to this combination, incl uding 8 of 14 patients with previously treated small cell lung carcinoma. CONCLUSIONS. The combination of paclitaxel, carboplatin, and topotecan is f easible, although only relatively low doses of all three drugs can be toler ated due to myelosuppression. This regimen showed a high level of activity in these patients with refractory cancer, and merits further investigation. Cancer 1999;85:1179-85, (C) 1999 American Cancer Society.