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


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.


CONCLUSIONS
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.
Delanian
Sylvie
S
Service d'Oncologie-Radiothérapie, Hôpital Saint-Louis, 1 Ave Claude Vellefaux, 75010 Paris, France. sylvie.delanian@sls.ap-hop-paris.fr
Porcher
Raphaël
R
Rudant
Jérémie
J
Lefaix
Jean-Louis
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001918:Brachytherapy / Q000009:adverse effects; D001943:Breast Neoplasms / Q000532:radiotherapy; D004359:Drug Therapy, Combination; D005260:Female; D006261:Headache / Q000139:chemically induced; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010431:Pentoxifylline / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000209:etiology; D011837:Radiation-Protective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D024505:Tocopherols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000975:Antioxidants; D011837:Radiation-Protective Agents; D024505:Tocopherols; D010431:Pentoxifylline