10-YEAR RESULTS OF A RANDOMIZED TRIAL EVALUATING PROLONGED LOW-DOSE ADJUVANT CHEMOTHERAPY IN NODE-POSITIVE BREAST-CANCER - A JOINT EUROPEAN-ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER, DUTCH BREAST-CANCER WORKING PARTY STUDY

Purpose: To investigate whether treatment with prolonged low-dose adjuvant chemotherapy could improve survival of patients with axillary node-positive breast cancer. Patients and Methods: Four hundred fifty-two patients with axillary node-positive breast cancer who received postoperative irradiation were prospectively randomised in a trial (European Organization for Research and Treatment of Cancer [EORTC] 09771) that compared surgery followed by prolonged low-dose chemotherapy versus surgery alone. Chemotherapy was given for a period of 2 years and consisted of monthly courses of cyclophosphamide 50 mg/m(2) orally on days 1 to 14, methotrexate 15 mg/m(2) intravenously on days 1 and 8, and fluorouracil 350 mg/m(2) intravenously on days 1 and 8 (CMF). Results: At a median follow-vp time of 10 years, the overall survival duration was significantly prolonged in the chemotherapy arm (hazards ratio, 0.75; 95% confidence interval, 0.56 to 0.99; P = .04). Ten-year overall survival rates (+/- SE) were 59% (+/- 3.6%) for the chemotherapy arm and 50% (+/- 3.7%) for the control arm. Time to local relapse was significantly prolonged in the chemotherapy arm (hazards ratio, 0.63; 95% confidence interval, 0.42 to 0.94; P = .02). Patients with one to three positive axillary nodes and patients with estrogen receptor-negative tumors especially benefited from chemotherapy. Toxicity was observed in 93% of patients. Conclusion: We conclude that prolonged low-dose adjuvant CMF con significantly prolong overall survival in patients with node-positive breast cancer. However, considering the fact that toxicity was still considerable despite reducing the dose of chemotherapy by 50%, we believe that conventionally dosed short-term regimens are preferable in the treatment of node-positive breast cancer.