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

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Abstract
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/m2orally every day for 1 year), fluorouracil (300 mg/m2intravenously [IV] weekly for 1 year), methotrexate (15 mg/m2IV weekly for 1 year), vincristine (0.625 mg/m2IV for 10 weeks), prednisone (30 mg/m2orally on Days 1–14, 20 mg/m2on Days 15–28, and 10 mg/m2on Days 29–42), or single‐agent chemotherapy with L‐PAM (5 mg/m2orally 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 andP= 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