RANDOMIZED TRIAL OF CYCLOPHOSPHAMIDE, METHOTREXATE, AND FLUOROURACIL CHEMOTHERAPY ADDED TO TAMOXIFEN AS ADJUVANT THERAPY IN POSTMENOPAUSAL WOMEN WITH NODE-POSITIVE ESTROGEN AND OR PROGESTERONE RECEPTOR-POSITIVE BREAST-CANCER - A REPORT OF THE NATIONAL-CANCER-INSTITUTE OF CANADA CLINICAL-TRIALS GROUP/

Purpose and Methods: By the mid 1980s, tamoxifen alone was considered standard adjuvant therapy for postmenopausal women with node-positive, estrogen receptor (ER)- or progesterone receptor (PgR)-positive breas t cancer. From 1984 through 1990, 705 eligible postmenopausal women wi th node-positive, ER- or PgR-positive breast cancer were randomized to a National Cancer Institute of Canada Clinical Trials Group (NCIC CTG ) study that compared tamoxifen 30 mg by mouth daily for 2 years (TAM) versus TAM plus chemotherapy with all-intravenous cyclophosphamide 60 0 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) given every 21 days for eight cycles (CMF). Results: There were no signific ant differences in overall survival, recurrence-free survival, locoreg ional recurrence-free survival, or distant recurrence-free survival be tween the tyro treatment arms, However, there was significantly greate r severe toxicity, which included leukopenia (P < .0001), nausea and v omiting (P < .0001), and thromboembolic events (P < .0001), us well as significantly more mild or greater toxicity, which included thrombocy topenia (P = .04), anemia (P = .02), infection (P = .0004), mucositis (P = .0001), diarrhea (P = .0001), and neurologic toxicity (P = .006), in women who received TAM plus CMF. Conclusion: The addition of CMF t o TAM adds no benefit and considerable toxicity in this group of women . (C) 1997 by American Society of Clinical Oncology.