Phase I–II study of high-dose etoposide in patients with refractory breast cancer
At conventional doses of 200-400 mg/m 2 every 3 weeks, etoposide has shown marginal activity in pretreated breast cancer patients [1], but it may have additive activity in combination with cisplatin [2] or cyclophosphamide [3], In other malignancies, its activity appears dose-dependent and doses of 1200 to 1500 mg/m ~ have been given without bone marrow support with severe, yet transient, myelosuppression [4]. Based on these considerations, high-dose etoposide has been incorporated in autologous bone marrow transplant regimens for breast cancer patients [5], although there are no data to substantiate its increased activity or additive effect at higher than standard doses in combination chemotherapy programs. In this study we attempted to define the nonhematologic maximum tolerated dose (MTD) and dose-limiting toxic effects of etoposide administered to breast cancer patients without autologous bone marrow support, and to assess its efficacy at higher-than-conventional doses.