Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a southwest oncology group study

BACKGROUND Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil plus vincristine and prednisone (CMFVP) was compared with single-agent L-phenylalanine mustard (L-PAM) for the treatment of patients with axillary lymph node positive primary breast carcinoma over 20-years of follow-up. METHODS Four hundred forty-one women with axillary lymph node positive breast carcinoma were randomized to receive either combination chemotherapy with cyclophosphamide (60 mg/m2 orally every day for 1 year), fluorouracil (300 mg/m2 intravenously [IV] weekly for 1 year), methotrexate (15 mg/m2 IV weekly for 1 year), vincristine (0.625 mg/m2 IV for 10 weeks), prednisone (30 mg/m2 orally on Days 1–14, 20 mg/m2 on Days 15–28, and 10 mg/m2 on Days 29–42), or single-agent chemotherapy with L-PAM (5 mg/m2 orally every day for 5 days every 6 weeks for 2 years) after undergoing surgery. Patients were stratified according to menopausal status and number of positive lymph nodes (1–3 positive lymph nodes or > 3 positive lymph nodes). Seventy-seven patients were ineligible. RESULTS The maximum follow-up is 24 years, with a median follow-up of 21.5 years. Disease free survival and overall survival were superior with CMFVP (two-sided log-rank test; P = 0.0008 and P = 0.007, respectively). For all patients, the estimated 20-year survival rate of patients who received CMFVP was 40% compared with 27% for patients who received L-PAM. There was a substantial survival benefit for CMFVP compared with L-PAM in the subsets of premenopausal patients and patients with four or more positive lymph nodes. The estimated 20-year survival rate for premenopausal women who received CMFVP was 49% compared with 33% for premenopausal women who received L-PAM. Among women with ≥ 4 positive lymph nodes, the estimated survival rate for patients who received CMFVP was 31% compared with 15% for patients who received L-PAM. Both regimens were tolerated well. Toxicity was more severe and frequent among patients who received CMFVP. CONCLUSIONS The authors conclude that, after 20 years of follow-up, adjuvant chemotherapy with CMFVP remains superior to L-PAM for the treatment of patients with lymph node positive breast carcinoma. Cancer 2003;97:21–9. © 2003 American Cancer Society. DOI 10.1002/cncr.10982