Future strategies for the treatment of advanced epithelial ovarian cancer using high-dose chemotherapy and autologous bone marrow support

The response and long-term disease-free survival rates with standard-dose salvage chemotherapy for advanced ovarian cancer are commonly reported to be less than 20 and 10%, respectively. More than 200 women with advanced, refractory, ovarian cancer have received high-dose chemotherapy regimens with autologous bone marrow support (ABMS) for their disease. A feature of the vast majority of the studies is the strikingly high response rates of 70-82% achieved when marrow-supported intensive therapy is administered to women with refractory ovarian cancer. Applying such high-dose therapy earlier in the disease course when the tumors are less resistant will likely produce durable antitumor effects. To further evaluate the effectiveness of high-dose therapy, the Southwest Oncology Group (SWOG) has initiated a phase II study for stage III/IV ovarian cancer with residual disease (microscopic up to 3 cm) following one cisplatin- or carboplatin-based induction regimen (SWOG 9106). Patients will be randomized to receive one of two high-dose regimens with ABMS: cyclophosphamide, cisplatin, and thiotepa or cyclophosphamide, carboplatin, and mitoxantrone. This initial trial is a feasibility study to evaluate whether such high-dose regimens can be given in a cooperative group setting to the ovarian cancer patient population. If the trial is successfully completed, one of the two regimens will be chosen (based on lesser toxicity) to use in a phase III randomized trial of high-dose therapy and ABMS versus standard therapy for high-risk ovarian cancer patients.