Originally published as JCO Early Release 10.1200/JCO.2005.02.4729 on October 31 2005

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Kinetics of Response to Long-Term Treatment Combining Pentoxifylline and Tocopherol in Patients With Superficial Radiation-Induced Fibrosis

From the Service d'Oncologie-Radiothérapie; Département Biostatistique Informatique Médicale/L'Institut National de la Santé et de la Recherche Médicale U717, Hôpital Saint-Louis, Paris; and Commissariat à l’Energie Atomique, Direction des Sciences du Vivant, and Département de Radiobiologie et de Radipathologie, Fontenay aux Roses, France

Address reprint requests to Sylvie Delanian, MD, PhD, Service d'Oncologie-Radiothérapie, Hôpital Saint-Louis, 1 Ave Claude Vellefaux, 75010 Paris, France; e-mail: sylvie.delanian{at}sls.ap-hop-paris.fr

PURPOSE: Significant regression of radiation (RT) -induced fibrosis (RIF) has been achieved after treatment combining pentoxifylline (PTX) and alpha-tocopherol (vitE). In this study, we focus on the maximum response, how long it takes to achieve response, and changes after treatment discontinuation.

PATIENTS AND METHODS: Measurable superficial RIF was assessed in patients treated by RT for breast cancer in a long-treatment (24 to 48 months) PTX-vitE (LPE) group of 37 patients (47 RIFs) and in a short-treatment (6 to 12 months) PTX-vitE (SPE) group of seven patients (eight RIFs). Between April 1995 and April 2000, women were treated with a daily combination of PTX (800 mg) and VitE (1,000 IU).

RESULTS: Combined PTX-vitE was continuously effective and resulted in exponential RIF surface area regression (–46% for LPE and –68% for SPE at 6 months, –58% for LPE and –69% for SPE at 12 months, –63% for LPE and –62% for SPE at 18 months, and –68% for LPE at 24 and 36 months). The mean estimated maximal treatment effect was 68% RIF surface area regression. The mean time to this effect was 24 months and was shorter (16 months) in more recent RIF (< 6 years since RT) than in older RIF (28 months; P = .0003). Symptom severity (Subjective Objective Medical Management and Analytic Evaluation score) was halved in both groups. After treatment discontinuation, mean RIF surface area at 1 year had increased by +40% in the SPE group (rebound) and +8.5% in the LPE group.

CONCLUSION: Under combined PTX-vitE treatment, RIF regression was exponential, with a two-thirds maximum response after a mean of 2 years. There was a risk of a rebound effect if treatment was too short. Long treatment ( 3 years) is recommended in patients with severe RIF.

Presented at the 15th Congress of Société Française de Radiothérapie Oncologique, Paris, France, November 3-5, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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