Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16

J Clin Oncol. 2008 Jan 1;26(1):37-43. doi: 10.1200/JCO.2007.11.8851. Epub 2007 Nov 19.

Abstract

Purpose: We conducted a multicenter, randomized trial to compare progression-free survival (PFS), overall survival (OS), and quality of life in women with metastatic breast cancer (MBC) receiving high-dose chemotherapy plus autologous stem-cell transplantation (ASCT; HDCT) compared with standard-dose therapy.

Patient and methods: Between April 1997 and December 2000, 386 women with MBC and no prior chemotherapy for metastatic disease were registered. After initial response to anthracycline- or taxane-based induction chemotherapy, 224 patients were randomly assigned: 112 to high-dose cyclophosphamide, mitoxantrone, and carboplatin chemotherapy and ASCT (HDCT), and 112 to standard therapy (ST). Median age was 47 years (range, 25 to 67 years). Thirty two percent of women randomly assigned had estrogen and progesterone receptor-negative breast cancer, 42% had visceral metastases, and 58% had bone metastases. Complete remission rates before random assignment were 11% for those receiving HDCT and 12% for those receiving ST.

Results: After a median follow-up of 48 months, 79 deaths were observed in the HDCT arm and 77 deaths were observed in the ST arm; seven patients (6%) in the HDCT arm died as a result of toxicity. The median OS was 24 months for the HDCT arm (95% CI, 21 to 35 months) and 28 months for ST (95% CI, 22 to 33 months; hazard ratio [HR], 0.9; 95% CI, 0.6 to 1.2; P = .43). PFS was 11 months for HDCT and 9 months for ST (HR, 0.6 in favor of HDCT; 95% CI, 0.5 to 0.9; P = .006).

Conclusion: HDCT did not improve OS in women with MBC when used as consolidation after response to induction chemotherapy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Middle Aged
  • Quality of Life
  • Treatment Outcome

Substances

  • Epirubicin
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil