Direct Gastrointestinal Toxicity of Flutamide: Comparison of Irradiated and Nonirradiated Cases

Abstract

Gastrointestinal (GI) side effects of flutamide in cases treated for advanced prostate cancer are well documented. Proposed mechanisms for these side effects include increased serum blood levels, direct vehicle effects and/or local toxicity. If local toxicity, the focus of this study, mediates GI side effects of flutamide then cases exposed to external beam radiation (XRT) should have more symptoms. We hypothesize that GI side effects of flutamide are not a direct local toxic effect resulting in a similar side effect profile for irradiated and nonirradiated cases. Thus, the present study compares GI effects of flutamide in irradiated and nonirradiated cases. We identified 106 of 440 cases from a prior flutamide dose comparison study as having undergone XRT (56 cases) or radical prostatectomy (50 patients). The prevalence of GI side effects (abdominal pain/distention, diarrhea, constipation, nausea/vomiting and anorexia) was tallied for each treatment group and/or dosing regimen, 250 mg every 8 hours or 500 mg daily. Chi-square analysis with Yates' correction was performed for statistical analysis. The overall prevalence in 106 cases of GI side effects with flutamide was 22%. Treatment specific differences revealed no differences between the XRT and radical prostatectomy groups at 21% and 22%, respectively. Furthermore, independent analysis of treatment groups for each distinct side effect and dosing regimen did not identify significant differences. Irradiated cases are not at greater risk for the development of GI side effects from flutamide, suggesting that drug induced local toxicity does not mediate GI distress.