Treatment of Lymphedema of the Arms and Legs with 5,6-Benzo-[alpha]-pyrone

John R. Casley-Smith, Robert Gwyn Morgan, Neil B. Piller

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    240 Citations (Scopus)


    Benzopyrones can reduce the volume of high-protein edema fluid by stimulating proteolysis. These compounds provide a method for removing excess protein and its consequent edema and reduce its clinical sequelae, such as chronic inflammation and secondary infections. We conducted a randomized, double-blind, placebo-controlled, crossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients with postmastectomy lymphedema of the arm and 21 patients with lymphedema of the leg of various causes. This agent is also known as 56 BaP, 1,2-benzopyrone, and coumarin, although it has no anticoagulant activity. The patients received 400 mg of the active drug or placebo, each for six months. During the placebo period, lymphedema often worsened, especially in the arms. Measurements of limb volume showed that the active drug reduced the mean amount of edema fluid in the arms from 46 percent above normal to 26 percent above normal (P<0.001) and the amount in the legs from 25 percent to 17 percent above normal (P<0.001). The circumference of the arms was reduced from 17 percent to 13 percent above normal, and the circumference of the legs from 11 percent to 7 percent above normal (P<0.001). The softness of the limb tissue was increased (P<0.001), and elevated skin temperatures were reduced (P<0.001). There were fewer attacks of secondary acute inflammation (P = 0.01). Bursting pains and feelings of hardness were decreased, as were feelings of tightness, tension, swelling, and heaviness; limb mobility also improved. The active drug was preferred to the placebo by 93 percent of the patients (P<0.001). Side effects – mild nausea or diarrhea – occurred in seven patients taking the active drug. None withdrew from the trial, and the side effects disappeared after the first month of therapy. 5,6-Benzo-[alpha]-pyrone results in slow but safe reduction of lymphedema of the extremities., Lymphedema, a form of high-protein edema, is a serious, long-lasting, and common problem; there are about 140 million cases throughout the world1,2. Correctly applied, physical methods of treatment rapidly reduce edema fluid,36 but they require intensive work and special training, and few centers offer them. Even then, only about half the fluid is removed; a year must elapse before half of the remainder can be removed. In a few cases surgery is beneficial, but often it is not1,4,7. Benzopyrones reduce lymphedema in both humans and animals1,816. These drugs have very low…

    Original languageEnglish
    Pages (from-to)1158-1163
    Number of pages6
    JournalNew England Journal of Medicine
    Issue number16
    Publication statusPublished - 14 Oct 1993

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