Phase I trial of multiple cycles of high-dose carboplatin, paclitaxel, andtopotecan with peripheral-blood stem-cell support as front-line therapy

Purpose: To determine the safety and feasibility of delivering multiple cyc les of front-line high-dose carboplatin, paclitaxel, and topotecan with per ipheral-blood stem-cell (PBSC) support. Patients and Methods: Patients were required to have a malignant solid tumo r for which they had received no prior chemotherapy. Mobilization of PBSC w as achieved with either filgrastim alone or in combination with cyclophosph amide and paclitaxel. Patients then received three or four cycles of high-d ose carboplatin (area under the concentration-time curve [AUC] 16), paclita xel (250 mg/m(2)), and topotecan (10-15 mg/m2), with the latter two agents administered as 24-hour infusions and supported with PBSC and filgrastim. C ycles were repeated every 28 days. Results: Twenty patients were enrolled onto the trial and were assessable f or toxicity and clinical outcome. Dose-limiting toxicities were stomatitis and prolonged hematopoietic recovery. The maximum-tolerated dose of topotec an was 12.5 mg/m(2) when given with highdose carboplatin and paclitaxel for three cycles. Four cycles were able to be given with a dose of topotecan o f 10 mg/m(2). The pharmacokinetics of each compound were not affected by th e other agents. Eleven (85%) of 13 patients with assessable disease respond ed. Conclusion: Multiple cycles of high-dose carboplatin, paclitaxel, and topot ecan can be safely administered with filgrastim and PBSC support. The recom mended doses for phase II study are carboplatin AUC 16, paclitaxel 250 mg/m 2, and topotecan 10 mg/m2. Trials are currently being conducted with this r egimen as front-line treatment in patients with advanced ovarian cancer and extensive small-cell carcinoma. This approach remains experimental and sho uld be used only in the context of a clinical trial.