Background Benzopyrones can reduce the volume of high-proteinedema fluid by stimulating proteolysis. These compounds providea method for removing excess protein and its consequent edemaand reduce its clinical sequelae, such as chronic inflammationand secondary infections.
Methods We conducted a randomized, double-blind, placebo-controlled,crossover trial of 5,6-benzo-[alpha]-pyrone in 31 patients withpostmastectomy lymphedema of the arm and 21 patients with lymphedemaof the leg of various causes. This agent is also known as 56BaP, 1,2-benzopyrone, and coumarin, although it has no anticoagulantactivity. The patients received 400 mg of the active drug orplacebo, each for six months.
Results During the placebo period, lymphedema often worsened,especially in the arms. Measurements of limb volume showed thatthe active drug reduced the mean amount of edema fluid in thearms from 46 percent above normal to 26 percent above normal(P<0.001) and the amount in the legs from 25 percent to 17percent above normal (P<0.001). The circumference of thearms was reduced from 17 percent to 13 percent above normal,and the circumference of the legs from 11 percent to 7 percentabove normal (P<0.001). The softness of the limb tissue wasincreased (P<0.001), and elevated skin temperatures werereduced (P<0.001). There were fewer attacks of secondaryacute inflammation (P = 0.01). Bursting pains and feelings ofhardness were decreased, as were feelings of tightness, tension,swelling, and heaviness; limb mobility also improved. The activedrug was preferred to the placebo by 93 percent of the patients(P<0.001). Side effects -- mild nausea or diarrhea -- occurredin seven patients taking the active drug. None withdrew fromthe trial, and the side effects disappeared after the firstmonth of therapy.
Conclusions 5,6-Benzo-[alpha]-pyrone results in slow but safereduction of lymphedema of the extremities.
Source Information
From the Henry Thomas Laboratory (Microcirculation Research), University of Adelaide, Adelaide (J.R.C.-S.); the Department of Surgery, Flinders Medical Centre, Bedford Park (R.G.M.); and the Faculty of Health Sciences, Flinders University, Bedford Park (N.B.P.) -- all in Australia.
Address reprint requests to Dr. Casley-Smith at the Henry Thomas Laboratory, University of Adelaide, Box 498 G.P.O., Adelaide, S.A. 5001, Australia.
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