A randomised prospective study of prolonged treatment with tocopherol and pentoxifylline, in addition to carbogen in the management of radiation late effects

Abstract

19682 Background: Pentoxifylline (PTX) and tocopherol (Vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation effects. To our knowledge, this is the first study to examine the clinical benefit of combination therapy with carbogen, tocopherol and pentoxifylline in the mitigation of late radiation effects. The optimal duration of PTX and tocopherol treatment has not been fully established. Therefore, we also studied short versus extended treatment duration. Methods: We conducted a phase II prospective randomised study of inhaled carbogen (95% oxygen + 5% carbon dioxide) over 90 minutes, 5 days per week for 3 weeks in addition to short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1,000 IU) orally once daily. All 18 patients received carbogen therapy. Patients with grade 3 toxicity post radical radiotherapy for a variety of cancer primaries were eligible for the trial. The primary endpoint was improvement in maximum Lent-Soma toxicity scores. Ethical approval was obtained. Results: Maximum Lent-Soma scores improved with treatment in six of the eighteen patients giving a 33% response rate. The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A (Fisher’s exact test: p = 0.321). Two patients in arm B had complete resolution of their symptoms, which was maintained at 2 and 3 years follow up. Conclusions: As late radiation effects are progressive by nature and have such a negative impact on quality of life in long-term cancer survivors, any treatment, which may ameliorate their symptoms, should be considered of benefit. This study confirms the benefit of prolonged treatment and we would recommend clinical use of these agents with treatment duration of at least 12 months, in the management of late radiation effects. No significant financial relationships to disclose.