Lack of effect of coumarin in women with lymphedema after treatment for breast cancer

N Engl J Med. 1999 Feb 4;340(5):346-50. doi: 10.1056/NEJM199902043400503.


Background: Lymphedema of the arms can be a serious consequence of local and regional therapy in women with breast cancer. Coumarin has been reported to be effective for the treatment of women with lymphedema; we undertook a study in which we attempted to replicate those findings.

Methods: We studied 140 women with chronic lymphedema of the ipsilateral arm after treatment for breast cancer. The women received 200 mg of oral coumarin or placebo twice daily for six months and then the other treatment for the following six months. The end points of the study consisted of the volume of the arm (calculated from measurements of hand and arm circumference) and the answers on a questionnaire completed by the patient about symptoms potentially related to lymphedema.

Results: The volumes of the arms at 6 and 12 months, were virtually identical, regardless of whether coumarin or placebo was given first. After six months, the average volume of the affected arm increased by 21 ml during placebo treatment and 58 ml during coumarin treatment (P=0.80). In addition, answers to patient-completed questionnaires were similar in the two treatment groups. After six months only 15 percent of the women in the coumarin group and 10 percent of those in the placebo group reported that the study medication had helped a moderate or large amount (P=0.19). Coumarin was well tolerated, except that it resulted in serologic evidence of liver toxicity in 6 percent of the women.

Conclusions: Coumarin is not effective therapy for women who have lymphedema of the arm after treatment for breast cancer.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery*
  • Chronic Disease
  • Combined Modality Therapy / adverse effects
  • Coumarins / adverse effects
  • Coumarins / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Lymphedema / drug therapy*
  • Lymphedema / etiology
  • Mastectomy
  • Middle Aged
  • Postoperative Complications / drug therapy*
  • Radiotherapy / adverse effects
  • Transaminases / blood
  • Treatment Failure


  • Coumarins
  • coumarin
  • Transaminases