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/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) 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.
Ejlertsen
Bent
B
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark. ejlertsen@rh.dk
Mouridsen
Henning T
HT
Jensen
Maj-Britt
MB
Andersen
Jørn
J
Andersson
Michael
M
Kamby
Claus
C
Knoop
Ann S
AS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007978:Levamisole / Q000008:administration & dosage* / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017697:Premenopause
D007978:Levamisole; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate