Okunieff P¹, Gerber L², Augustine E², Hicks J², Cornelison T³, Altemus R³, Coleman N³, Naydich B³, Ding I³, Abraham E³, Smith J³; University of Rochester, Department of Radiation Oncology¹, Rochester, NY; National Institutes of Health, Clinical Center, Rehabilitation Medicine Department², National Cancer Institute, Radiation Oncology Branch³, Bethesda, MD.

PURPOSE: The purpose of this study was to explore the role of pentoxifylline, used as an anti-cytokine therapy, on the alleviation of functional disability caused by radiation induced fibrosis. BACKGROUND: The fibrotic sequelae of radiation remain the most important dose limiting toxicity of radiation therapy. Tumor necrosis factor alpha (TNFα), transforming growth factor beta (TGFβ), and basic fibroblast growth factor (FGF2), which are abnormally elevated in irradiated tissues, may partly mediate fibrovascular injury. Pentoxifylline inhibits TNFα synthesis and secretion, and may also modulate FGF2 production. SUBJECTS: We studied the effects of pentoxifylline in a group of 30 patients who sustained delayed effects of radiation induced fibrosis. Patients were age 18 to 78 years (median 56 years), and were 1 to 29 years (mean 10.1 years) status post 4000 to 8402 (mean 5909) cGy tumor irradiation dose. METHODS: The trial followed a prospective, open label design of pentoxifylline 400 mg orally t.i.d. for 8 weeks followed by 8 weeks off-drug. Patients underwent assessment at baseline, eight weeks, and 16 weeks. Quantitative cytokine assay were performed using enzyme linked immunosorbent assay kits. Range of motion (ROM), muscle strength, limb edema, pain and tissue compliance were measured. Patients were evaluated for toxicity to digestive system and central nervous system. ANALYSIS: Objective clinical success was considered met if ≥ 25% of patients improved ≥ one rank of the 4-point rehabilitation medicine severity scale (normal, mild, moderate, severe). Cytokine levels were correlated with clinical outcome using student’s t-test and chi-square analysis for trend. RESULTS: After 8 weeks of pentoxifylline improvements were noted: 20/23 patients had improved ROM, 11/19 had improved strength, 5/7 had decreased edema, 7/9 had decreased pain, and 14/24 had improved tissue compliance. Improvements deteriorated by week 16: 10/20 had decreased ROM, 2/11 had decreased strength, 1/5 had increased edema, 7/9 had increased pain, and 5/14 had decreased tissue compliance. CONCLUSIONS: Pentoxifylline improves some impairments associated with radiation induced soft tissue damage. ROM was most responsive to treatment. This effect depends upon continued use of pentoxifylline. The improvements correlate with reduction in FGF2. FUNDING SOURCE: Yes - National Cancer Institute.

Reprint Information
Requests for reprints should be directed to the corresponding author of the article. Students and other academic customers may receive permission to reprint copyrighted material from Physical Therapy by contacting the Copyright Clearance Center Inc, 222 Rosewood Dr, Danvers, MA 01923. Similar inquiries by all others should be made to the APTA Editorial Office, Attn: Physical Therapy.