TREATMENT OF LYMPHEDEMA OF THE ARMS AND LEGS WITH 5,6-BENZO-[ALPHA]-PYRONE

Background. Benzopyrones can reduce the volume of high-protein edema f luid by stimulating proteolysis. These compounds provide a method for removing excess protein and its consequent edema and reduce its clinic al sequelae, such as chronic inflammation and secondary infections. Me thods. We conducted a randomized, double-blind, placebo-controlled, cr ossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients with postmast ectomy lymphedema of the arm and 21 patients with lymphedema of the le g of various causes. This agent is also known as 56 BaP, 1,2-benzopyro ne, and coumarin, although it has no anticoagulant activity. The patie nts received 400 mg of the active drug or placebo, each for six months . Results. During the placebo period, lymphedema often worsened, espec ially in the arms. Measurements of limb volume showed that the active drug reduced the mean amount of edema fluid in the arms from 46 percen t 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 cir cumference of the arms was reduced from 17 percent to 13 percent above normal, and the circumference of the legs from 11 percent to 7 percen t above normal (P<0.001). The softness of the limb tissue was increase d (P<0.001), and elevated skin temperatures were reduced (P<0.001). Th ere were fewer attacks of secondary acute inflammation (P = 0.01). Bur sting pains and feelings of hardness were decreased, as were feelings of tightness, tension, swelling, and heaviness; limb mobility also imp roved. The active drug was preferred to the placebo by 93 percent of t he patients (P<0.001). Side effects - mild nausea or diarrhea - occurr ed in seven patients taking the active drug. None withdrew f rom the t rial, and the side effects disappeared after the first month of therap y. Conclusions. 5,6-Benzo-[alpha]-pyrone results in slow but safe redu ction of lymphedema of the extremities.