Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

BACKGROUND:This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. METHODS:A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. RESULTS:The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p = .96) or grade 2 gastrointestinal (p = .75), genitourinary (p = .44), and sexual (p = .29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p = .03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p = .005). A nonsignificant trend (p = .09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. CONCLUSIONS:Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.