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

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.
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).
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.
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.
AuthorsBent Ejlertsen, Henning T Mouridsen, Maj-Britt Jensen, Jørn Andersen, Michael Andersson, Claus Kamby, Ann S Knoop,
JournalCancer (Cancer) Vol. 116 Issue 9 Pg. 2081-9 (May 1 2010) ISSN: 0008-543X [Print] United States
PMID20186830 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright(c) 2010 American Cancer Society.
Chemical References
  • Levamisole
  • Cisplatin
  • Fluorouracil
  • Methotrexate
  • Adenocarcinoma (drug therapy, mortality, pathology, radiotherapy)
  • Administration, Oral
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
  • Breast Neoplasms (drug therapy, mortality, pathology, radiotherapy)
  • Chemotherapy, Adjuvant
  • Cisplatin (administration & dosage, adverse effects)
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Fluorouracil (administration & dosage, adverse effects)
  • Humans
  • Levamisole (administration & dosage, adverse effects)
  • Methotrexate (administration & dosage, adverse effects)
  • Middle Aged
  • Premenopause

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