Adjuvant chemotherapy for node-positive breast cancer: a retrospective comparison of two different regimens of cyclophosphamide, methotrexate and 5-fluorouracil

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Adjuvant chemotherapy after surgery for early breast cancer has been shown to reduce disease recurrence and mortality. The effectiveness of ‘classical’ oral CMF (oral cyclophosphamide on days 1 to 14, combined with intravenous methotrexate and 5-fluorouracil given intravenously on days 1 and 8, repeated every 28 days) is well established. Modified protocols of CMF (where all three drugs are given as bolus intravenous injections once or twice every 3 or 4 weeks) have been used in many centres, because of a perceived greater convenience, better compliance, and reduced toxicity. Many such intravenous CMF (IV CMF) protocols deliver somewhat lower total drug doses, at a lower dose intensity, than classical oral CMF. It is important to know if there is any resultant reduction in efficacy with such regimens. This study compares the delivered dose intensity, efficacy and toxicity of the classical oral regimen with that of a modified CMF regimen delivered intravenously at 3-weekly intervals for six cycles. We performed a retrospective study of women with axillary node-positive breast cancer treated at our centre, between January 1980 and December 1991, in the adjuvant setting with either classical oral CMF ( n=70) or with an IV CMF protocol ( n=200). Although the mean delivered dose intensity was higher in the oral CMF than in the IV CMF group, we detected no difference in disease-free or overall survival at 5 years. Alopecia and weight gain were reported more frequently in the oral CMF group than in the IV CMF group. Nausea and emesis were also more severe in the oral group, although this may reflect, at least in part, the use of different antiemetics in the two cohorts. Although many patients are willing to tolerate quite severe side-effects for relatively small additional gains in survival, for others, reduced side-effects and fewer clinic attendances may make IV CMF an attractive option. Our data suggest that IV CMF remains a reasonable alternative for such patients.