Bonadonna G et al. (2005) 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ [10.1136/bmj.38314.622095.8F]

Bonadonna and colleagues have recently reported on their long-term experience of using cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as adjuvant treatment in women with breast cancer. They show that the 'moderate but worthwhile' benefits of this therapy are durable and are not associated with detrimental effects.

Starting in 1973, the investigators carried out three clinical trials and one observational study at the Istituto Nazionale Tumori in Milan, Italy. All the studies included women with unilateral breast cancer who underwent radical mastectomy or conservative surgery and full axillary clearance. Patients received either 6 or 12 cycles of adjuvant CMF or no further treatment after surgery.

After a median follow-up of 28.5 years, the first randomized trial showed that overall survival and relapse-free survival were superior in women who received CMF therapy compared with those who did not, and that the major effect of therapy was a reduced incidence of distant metastases. Further analysis of these data and of the subsequent trials showed that 6 cycles of CMF was equally as effective as 12 cycles, and that the risk of relapse was also reduced in women with node-negative and estrogen receptor-negative tumors.

Acknowledging the role of new drugs, such as anthracyclines and taxanes, Bonadonna et al. conclude that the CMF regimen has added considerably to breast cancer treatment and is beneficial over the long term.