Cyclophosphamide,methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high‐risk,premenopausal breast cancer

BACKGROUND:

The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single‐agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) against no adjuvant systemic therapy in high‐risk breast cancer patients. The authors report the results from that trial after a potential follow‐up of 25 years.

METHODS:

Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m² on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m² on Days 1 through 14 plus methotrexate 30 mg/m² and fluorouracil 500 mg/m² intravenously on Days 1 and 8 every 4 weeks for 12 cycles (the CMF arm).

RESULTS:

The 10‐year invasive disease‐free survival (IDFS) rate was 38.6% in the control arm compared with 55.5% in the C arm, 48.8% in the CMF arm, and 35.2% in the levamisole arm. Compared with the control arm, the hazard ratio for an IDFS event was 0.62 in the C arm (P = .001) and 0.70 in the CMF arm (P = .01). The hazard ratio for death was 0.70 in both the C arm (P = .02) and the CMF arm (P = .02) at 10 years, and the overall survival (OS) benefit was maintained during 25 years of follow‐up. No significant differences were observed in IDFS or OS between the C arm and the CMF arm or between the levamisole arm and the control arm.

CONCLUSIONS:

Compared with controls, both cyclophosphamide and CMF significantly improved disease‐free survival and OS, and the benefits persisted for at least 25 years in premenopausal patients who had high‐risk breast cancer. Cancer 2010. © 2010 American Cancer Society.