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To assess the optimal duration and method of administration of adjuvant cyclophosphamide, methotrexate and 5‐fluorouracil (CMF) chemotherapy, 116 patients with positive axillary nodes after total mastectomy and axillary dissection were reviewed retrospectively. CMF was administered in three progressively shorter regimens, which consisted of oral CMF for either 12 or six cycles and intravenous (i.v.) CMF for six cycles. Median follow‐up for surviving patients was 62 months. The three groups were matched for major prognostic factors. There was no advantage in using more than six cycles of adjuvant CMF. Thre was an improved crude 3 year disease‐free survival (84 vs 65%, P= 0.05) and a trend towards improved overall survival (92 vs 85%, P= NS) in patients treated with six cycles of oral CMF compared with i.v. CMF. Survival rates were not significantly different beyond 3 years. Leucopenia and alopecia were more severe with oral CMF (P < 0.01), and compliance worse with oral CMF × 12 (P= 0.01). Since the data suggest that i.v. CMF is at least as equal as oral CMF a randomized controlled trial should be undertaken.

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