Randomized, Placebo-Controlled Trial of Combined Pentoxifylline and Tocopherol for Regression of Superficial Radiation-Induced Fibrosis

Abstract

Purpose: Radiation-induced fibrosis (RIF) is a rare morbid complication of radiotherapy, without an established method of management. RIF treatment with a combination of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) was recently prompted by the good results of a clinical trial and an animal study. The present double-blind, placebo-controlled, monocentric study was designed to assess the efficacy of this combination in treating RIF sequelae. Patients and Methods: Twenty-four eligible women with 29 RIF areas involving the skin and underlying tissues were enrolled from December 1998 to April 2000. These patients, previously irradiated for breast cancer, were randomly assigned to four balanced treatment groups: (A) 800 mg/d of PTX and 1,000 U/d of Vit E; (B) PTX plus placebo; (C) placebo plus Vit E; and (D) placebo-placebo. The main end point measure was the relative regression of measurable RIF surface after 6 months of treatment. Assessment was completed by depth (with ultrasonography) and associated symptom measures. Results: Twenty-two patients with 27 RIF areas were analyzed at 6 months. Mean RIF surface regression was significant with combined PTX/Vit E versus double placebo (60% ± 10% v 43% ± 17%; P = .038). The median slope for the speed of RIF surface area and volume regression was significantly higher for group A than groups B, C, and D. All treatments were well tolerated. Conclusion: Six months’ treatment of combined PTX/Vit E can significantly reduce superficial RIF. Synergism between PTX and Vit E is likely, as treatment with each drug alone is ineffective, but these results require confirmation in larger series.