4-STEP HIGH-DOSE SEQUENTIAL CHEMOTHERAPY WITH DOUBLE HEMATOPOIETIC PROGENITOR-CELL RESCUE FOR METASTATIC BREAST-CANCER

Purpose: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast c ancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose seq uential chemotherapy (HDSC) with double autologous hematopoietic proge nitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment wit h cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with c losely timed repeated courses of several non-cross-resistant agents. P atients and Methods: The treatment plan included CY 7 g/m(2), followed by GM-CSF 5 to 7 mu g/kg/d administered by continuous intravenous (IV ) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) har vest; mitoxantrone (NOV) 60, 75, or 90 mg/m(2) plus melpholan (L-PAM) 140 to 180 mg/m(2) with hematopoietic rescue; methotrexate (MTX) 8 g/m (2) plus vincristine (VCR) 1.4 mg/m(2); and etoposide (VP-16) 1.5 g/m( 2) plus carboplatin (PP) 1.5 g/m(2) with hematopoietic rescue. Results : All 15 patients enrolled completed the entire treatment and there we re no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/mu L and platelet count less than 20,000/mu L were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after V P-16 plus PP. The main nonhematologic toxicity was mucositis, while or gan toxicity was mild and reversible. Conclusion: This regimen is feas ible, with acceptable toxicity. GM-CSF and PBPCs Rove a pivotal role, as they hasten hematololic reconstitution, abate toxicity, and allow r apid recycling. J Clin Oncol 13:840-846. (C) 1995 by American Society of Clinical Oncology.