Adjuvant Metronomic CMF in a Contemporary Breast Cancer Cohort: What's Old Is New

Clin Breast Cancer. 2015 Oct;15(5):e277-85. doi: 10.1016/j.clbc.2015.04.002. Epub 2015 Apr 24.

Abstract

Background: Commonly used adjuvant systemic therapies harbor high rates of severe short-term and long-term side effects but are often justified to patients because of curative intent in early-stage breast cancer. One of the oldest and least toxic adjuvant regimens, CMF (oral cyclophosphamide given with intravenous methotrexate and 5-fluorouracil), has been largely abandoned because of the perception that it underperforms for survival outcomes compared with modern regimens containing anthracycline and/or taxanes.

Materials and methods: To address this misperception, we performed a review of all consecutive breast cancer patients at the Seattle Cancer Care Alliance over the past decade who received 6 months of adjuvant CMF as their sole chemotherapy regimen and determined rates for relapse-free survival (RFS), overall survival (OS), and major organ toxicity. From January 2003 to August 2013, 248 patients (median age of 52 years at the start of chemotherapy) met criteria for inclusion in this series and had a median follow-up of 67 months.

Results: RFS and OS at 5 years was 94.5% (91.3%-97.9%) and 98% (96%-100%), respectively. The only major organ toxicity that occurred in > 5% of patients was Grade 3 neutropenia (18.1%, 24 patients). One patient died during therapy from pneumocystis pneumonia attributed to previously undiagnosed AIDS.

Conclusion: In a modern cohort of patients thoroughly characterized for Grade and hormone receptor status, CMF was a well-tolerated and effective adjuvant regimen for early-stage breast cancer and should be considered for appropriately selected patients.

Keywords: Adjuvant chemotherapy; Cyclophosphamide; Fluorouracil; Hormone-receptor positive; Methotrexate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasm Staging

Substances

  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen