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 r esulted in significant tumor responses in the majority of patients wit h metastatic breast cancer, a minority of which are durable. To improv e on these results, we are developing high-dose preparative regimens w hich may be given in successive cycles, each with autologous bone marr ow transplantation (ABMT), over a short duration. In this report, 44 p atients with metastatic breast cancer were treated with thiotepa (tota l dose: 900 mg/m2) and mitoxantrone (MT), administered in a dose-escal ation fashion, with ABMT. The dose-limiting non-hematologic toxicity o f mitoxantrone was cardiotoxicity, with the maximum tolerated dose bei ng 50 mg/m2 Mucositis and pneumonia were also frequent treatment-relat ed side-effects. The overall tumor response rate was 49% in this heavi ly pre-treated group of patients. We are currently evaluating the toxi city and efficacy of tandem non-cross-resistant transplant regimens, u sing the MT combination for the second cycle of therapy, in patients w ith metastatic breast cancer sensitive to standard dose chemotherapy.