Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: The International Breast Cancer Study Group Trial VII

Purpose: Information on the tolerability and efficacy of adjuvant chemoendo crine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Tria l VII. Patients and Methods: Postmenopausal women with operable, node-positive bre ast cancer were randomized to receive either tamoxifen atone for 5 years (3 06 patients) or tamoxifen plus three consecutive cycles of classical cyclop hosphamide (100 mg/m(2) orally days 1 to 14), methotrexate (40 mg/m(2) intr avenous days 1 and 8), and fluorouracil (600 mg/m(2) intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. Results: Among the 299 patients who received at least one dose of CMF, wome n 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P = .004), More women in the o lder age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5 %, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively), Old er patients also received less than their expected CMF dose compared with y ounger postmenopausal women (P = .0008). The subjective burdens of treatmen t, however, were similar for younger and older patients based on quality-of -life measurer (performance status, coping, physical wellbeing, mood, and a ppetite), Far older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [Cl], 0.65 to 1.52; P = .99). For young er patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% Cl, 0.53 to 0.91; P = .008), hut the test for heterogeneity of CMF eff ect according to age group was not statistically significant, The reduced e ffectiveness of CMF among older women could not be attributed to doss reduc tions according to dose received. Conclusion: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer p atients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for hig h-risk elderly patients. (C) 2000 by American Society of Clinical Oncology.