Adjuvant chemotherapy with and without radiotherapy in stage II breast cancer

The influence of several variables on the effectiveness of adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy given to 87 patients with stage II breast cancer was retrospectively analyzed. CMF was given in optimal doses (greater than or equal to 85% of the planned dose) to 17% of the patients; in intermediate doses (66-84% of the planned dose) to 50% of the patients; and in low doses (less than or equal to 65% of the planned dose) to 33% of the patients. Radiotherapy before CMF was given to 68% of the patients; simultaneous radio- and chemotherapy to 17% of the patients; and the remaining 15% received CMF only. At a median follow-up of 8 yr, 61% of the patients were still alive; 54% of them were disease-free. Patients receiving radio- and chemotherapy concomitantly had a higher relapse-free survival (RFS) than those given both treatments sequentially (77% versus 46%; P = 0.05). Dose levels of CMF did not influence RFS. Delay in initiation of CMF, mainly due to the administration of prior radiotherapy was deleterious: patients started on CMF within 3 months of diagnosis had a 77% 8 yr RFS, as compared with 44% for those with a delay of over 3 months (P = 0.01). No differences in local relapse rates were observed between irradiated and non-irradiated patients, although 87% of all distant failures occurred in patients who received radio- and chemotherapy sequentially. The data of this study indicate that delay in onset of CMF is deleterious, and can be avoided by the simultaneous administration of both treatment modalities, since this approach was well tolerated, without significant myelotoxicity.