Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis

J Clin Oncol. 2005 Dec 1;23(34):8570-9. doi: 10.1200/JCO.2005.02.4729. Epub 2005 Oct 31.

Abstract

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants / adverse effects
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use*
  • Brachytherapy / adverse effects
  • Breast Neoplasms / radiotherapy
  • Drug Therapy, Combination
  • Female
  • Headache / chemically induced
  • Hot Flashes / chemically induced
  • Humans
  • Kinetics
  • Middle Aged
  • Nausea / chemically induced
  • Pentoxifylline / adverse effects
  • Pentoxifylline / pharmacokinetics
  • Pentoxifylline / therapeutic use*
  • Radiation Pneumonitis / drug therapy*
  • Radiation Pneumonitis / etiology
  • Radiation-Protective Agents / adverse effects
  • Radiation-Protective Agents / pharmacokinetics
  • Radiation-Protective Agents / therapeutic use*
  • Time Factors
  • Tocopherols / adverse effects
  • Tocopherols / pharmacokinetics
  • Tocopherols / therapeutic use*
  • Treatment Outcome

Substances

  • Antioxidants
  • Radiation-Protective Agents
  • Tocopherols
  • Pentoxifylline