Dose escalation of mitoxantrone given with thiotepa and autologous bone marrow transplantation for metastatic breast cancer.

High-dose chemotherapy given with autologous bone marrow support has resulted in significant tumor responses in the majority of patients with metastatic breast cancer, a minority of which are durable. To improve on these results, we are developing high-dose preparative regimens which may be given in successive cycles, each with autologous bone marrow transplantation (ABMT), over a short duration. In this report, 44 patients with metastatic breast cancer were treated with thiotepa (total dose: 900 mg/m2) and mitoxantrone (MT), administered in a dose-escalation fashion, with ABMT. The dose-limiting non-hematologic toxicity of mitoxantrone was cardiotoxicity, with the maximum tolerated dose being 50 mg/m2 Mucositis and pneumonia were also frequent treatment-related side-effects. The overall tumor response rate was 49% in this heavily pre-treated group of patients. We are currently evaluating the toxicity and efficacy of tandem non-cross-resistant transplant regimens, using the MT combination for the second cycle of therapy, in patients with metastatic breast cancer sensitive to standard dose chemotherapy.