RANDOMIZED 2X2 TRIAL EVALUATING HORMONAL TREATMENT AND THE DURATION OF CHEMOTHERAPY IN NODE-POSITIVE BREAST-CANCER PATIENTS

Purpose: In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness o f three versus six cycles of 500 mg/m(2) cyclophosphamide, 40 mg/m(2) methotrexate, and 600 mg/m(2) flourouracil (CMF) on day 1 and 8 starti ng perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overal l survival between the different treatment modalities. Patients and Me thods: During 5 years, 41 institutions randomized 473 patients (3 x CM F: 145; 3 x CMF + TAM: 93; 6 x CMF: 144; 6 x CMF + TAM: 91). Until Mar ch 31, 1992, median follow-up time was 56 months with 197 events for d isease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference correspo nding to a relative risk (RR) of 0.67 for recurrence-free survival. Tr eatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis. Results: No signif icant difference in recurrence-free survival observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI] , 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.9 0 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar result s were obtained for overall survival. The multivariate analysis reveal ed a significant prognostic impact of the number of positive lymph nod es and the progesterone receptor level on recurrence-free survival. Co mpliance with chemotherapy within the range of 85% to 115% of the targ et dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was repo rted for 141 patients (93%). Conclusion: At this stage of follow-up, s ix courses of CMF are not superior to three courses with respect to re currence-free survival.