HIGH-DOSE BUSULFAN AND CYCLOPHOSPHAMIDE FOLLOWED BY AUTOLOGOUS BONE-MARROW TRANSPLANTATION AND OR PERIPHERAL-BLOOD PROGENITOR-CELL RESCUE FOR METASTATIC BREAST-CANCER/

High doses of combination alkylating agents have shown promise in the treatment of breast cancer but are complicated by significant toxicity . Busulfan and cyclophosphamide (BuCy) is a high-dose combination alky lating agent regimen that is well-tolerated when given for hematologic malignancy. We prospectively studied the effects of BuCy followed by autologous bone marrow transplant (ABMT) or peripheral blood progenito r cell (PBPC) rescue in 21 patients with metastatic breast cancer who had responded to either standard chemotherapy or radiotherapy. The mea n patient age was 44 years, Nine patients were either estrogen- or pro gesterone-receptor positive, ten were negative, and two were unknown. Fourteen patients had local recurrence, ten had bone metastases, six h ad visceral disease, and two had a nonlocal soft tissue recurrence, Bu sulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCy2) was given and f ollowed by either ABMT, PBPC rescue, or both. Grade III to IV extramye loid toxicity occurred in 6 (29%) patients, One patient died of hepati c venoocclusive disease but there was no other treatment-related morta lity. Pulmonary infiltrates with hypoxia of uncertain origin developed in 2 patients after discharge. Of the 10 patients with measurable dis ease, 4 had complete responses, and 3 had partial responses to high-do se therapy for a total response rate of 70%. The estimated 2-year dise ase-free survival is 25% (95% CI = 6% to 44%). Our study found BuCy to be a well-tolerated preparative regimen for ABMT in the treatment of patients with metastatic breast cancer.