High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: A new regimen for the treatment of advanced ovarian cancer

Objective. The goal of this study was to determine the optimal dose of topo tecan when used in combination with high-dose melphalan and cyclophosphamid e (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer. Methods. Fifty-three patients with persistent or recurrent ovarian cancer w ere treated. Disease status at study entry included: platinum-sensitive rec urrent disease (15 patients), platinum-resistant or refractory recurrent di sease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 t o -2. Peripheral blood stem cells were infused on Day 0. Results. The optimal topotecan dose selected for future trials was 4.0 mg/m (2)/day x 5 days. The regimen had acceptable toxicity with no regimen-relat ed death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with meas urable or evaluable disease was 93%. Median survival has not yet been reach ed, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive. Conclusion. With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regi men has acceptable toxicity and produces high response rates. In the settin g of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian can cer. (C) 2001 Academic Press.