Four-step high-dose sequential chemotherapy with double hematopoietic progenitor-cell rescue for metastatic breast cancer

F. Patrone, A. Ballestrero, F. Ferrando, F. Brema, L. Moraglio, M. Valbonesi, P. Basta, R. Ghio, M. Gobbi, M. Sessarego

Research output: Contribution to journalArticlepeer-review


Purpose: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (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 sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. Patients and Methods: The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 μg/kg/d administered by continuous intravenous (IV) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. Results: All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/μL and platelet count less than 20,000/μL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main nonhematologic toxicity was mucositis, while organ toxicity was mild and reversible. Conclusion: This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.

Original languageEnglish
Pages (from-to)840-846
Number of pages7
JournalJournal of Clinical Oncology
Issue number4
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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