High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial

J Clin Oncol. 1995 Oct;13(10):2483-9. doi: 10.1200/JCO.1995.13.10.2483.


Purpose: The aims of this study were to compare in a randomized trial the results of high-dose versus conventional-dose chemotherapy as first-line treatment for metastatic breast cancer. The comparison included complete response (CR) rate, duration of response, and duration of survival.

Patients and methods: Ninety patients were entered onto a study to compare two cycles of high-dose cyclophosphamide 2.4 g/m2, mitoxantrone 35 to 45 mg/m2, and etoposide (VP16) 2.5 g/m2 (HD-CNV) versus six to eight cycles of conventional-dose cyclophosphamide 600 mg/m2, mitoxantrone 12 mg/m2, and vincristine 1.4 mg/m2 (CNV) as first-line treatment for metastatic breast cancer. The high-dose regimen included either autologous bone marrow or peripheral-blood stem-cell rescue. All 90 patients are assessable.

Results: The response rates were significantly different. The overall response rate for HD-CNV was 43 of 45 (95%), with 23 of 45 patients (51%) achieving CR. Twenty-four of 45 patients (53%) who received conventional CNV have responded, with only two patients achieving CR. Both duration of response and duration of survival were significantly longer for patients, who received HD-CNV. Toxicity of the high-dose therapy was moderate in most patients. Grade 2 to 3 mucositis and hematologic suppression that required supportive treatment was universal, but hematologic recovery to a neutrophil count more than 500/microL and platelet count more than 40,000/microL occurred at day 18 (median) after therapy.

Conclusion: HD-CNV appears to be a promising schedule that results in a significant proportion of CRs and increased survival in patients with metastatic breast cancer.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Retracted Publication

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation
  • Bone Neoplasms / secondary
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Confidence Intervals
  • Cyclophosphamide / administration & dosage
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Heart Diseases / chemically induced
  • Hematologic Diseases / chemically induced
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Length of Stay
  • Mitoxantrone / administration & dosage
  • Neutropenia / chemically induced
  • Neutropenia / therapy
  • Pilot Projects
  • Platelet Count / drug effects
  • Remission Induction
  • Survival Rate
  • Vincristine / administration & dosage


  • Antineoplastic Agents
  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Mitoxantrone

Supplementary concepts

  • CNV protocol
  • HD-CNV protocol