Adjuvant chemotherapy for early breast cancer: Is cyclophosphamide, methotrexate and 5‐fluorouracil still the standard?

Abstract

AbstractBackground: Oral cyclophosphamide, methotrexate and 5‐fluorouracil (CMF) was one of the first combination chemotherapy regimens used as adjuvant chemotherapy for early breast cancer. The value of CMF in reducing both recurrence and mortality from early breast cancer has been firmly established by the overviews of randomized trials of polychemotherapy, which have used CMF as their standard. The purpose of this review is to review the usage of oral CMF and the variants of CMF and to compare both the activity and side‐effects of CMF with more modern adjuvant chemotherapy regimens.Results: There are many variants of CMF but oral (or classical) CMF is probably more effective than intravenous (i.v.) CMF, at least in metastatic disease. When oral CMF is used in early breast cancer it reduces the annual hazard of recurrence by 24% and the annual hazard of mortality by 14% overall, although it appears more effective in younger patients. Anthracycline‐based regimens are more effective for reduction of recurrence and mortality than CMF but are associated with more severe acute toxicities and potentially greater risks of long‐term toxicities. Taxane‐based regimens have not been compared with CMF directly; however, in comparison with anthracycline‐based regimens, the early information suggests that taxane‐based regimens may be even more effective. The acute toxicities of taxane‐based regimens are probably less severe than anthracycline‐based regimens, but their long‐term toxicities are less well defined.Conclusion: Oral CMF as adjuvant chemotherapy for early breast cancer is the standard by which newer regimens are compared. Although newer regimens appear more effective than CMF, they may be associated with greater acute and potentially greater long‐term toxicities than CMF. Thus, CMF remains the standard by which future regimens should be judged, either directly or indirectly.