Adjuvant CMF for breast cancer – pro

Lay Summary: CMF is an older regimen that has alrgely been supplanted by anthracycline containing regimens. However, it is still used when the patient would not accept alopecia or wishes a ‘gentler’ therapy.

A 1992 “overview” showed that chemotherapy lowers the annual odds of recurrence by 28% in perated breast cancer, with an absolute benefit of 8.4% at 10 years of follow-up. A 16% reduction in the annual risk of death was seen, resulting in 6.3% fewer deaths overall after 10 years . Chemotherapy combinations were superior to single agents, and CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) was the chemotherapy regimen most well represented. Additional drugs beyond CMF did not appear to improve outcomes, and two “standard” versions of CMF (all i.v. at 21-day intervals or day 1 and 8 i.v. treatment with methotrexate and 5-fluorouracil with oral cyclophosphamide on days 1 through 14) are most widely used, in either case for about six months. Longer durations of therapy have not been shown to be better, and a single cycle of treatment is inferior.

CMF is one of the oldest and most established breast cancer regimens. However, Methotrexate is FDA approved only for sarcoma, cyclophphosphamide has not FDA indications, and 5FU is approved to prolong survival in colon cancer in combination with leucovorin. The reason for this is that these agents predated the establishment and mandate of the FDA and were grandfathered without FDA indications for breast cancer.
CMF remains a reasonable option, as long as the patient is advised that modern regimens have been demonstrated to give about a 20% relative improvement. For some patients. the reduced toxicities make it an acceptable trade-off.

G. Bonadonna, A. Moliterni, M. Zambetti, M. G. Daidone, S. Pilotti, L. Gianni, and P. Valagussa
30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study
BMJ, January 29, 2005; 330(7485): 217.

NCCN.ORG, Breast Cancer, 2013

E. Munzone et al, CMF revisited in the 21st century Ann Oncol mdr309 first published online June 29, 2011 doi:10.1093/annonc/mdr309

G. N Hortobagyi Progress in Systemic Chemotherapy of Primary Breast Cancer: an Overview
J Natl Cancer Inst Monographs, December 1, 2001; 2001(30): 72 – 79.

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