Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer

Background:despite palliative benefits and psa responses, the objective clinical impact of daily oral prednisone (p) for metastatic castration-resistant prostate cancer (mcrpc) is unknown. we performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent p to evaluate its impact on overall survival (os) and toxicities.methods:individual patient data from control arms of randomized trials of men with mcrpc who received placebo or p+placebo post docetaxel were eligible for analysis. the impact of p on os and severe toxicities was investigated in cox regression models adjusted for known prognostic factors. statistical significance was defined as p<0.05 and all tests were two sided.results:data from the control arms of two randomized phase iii trials were available totaling 794 men: the cou-aa-301 trial (n=394) administered p plus placebo and the ca184-043 trial (n=400) administered placebo alone. p plus placebo was not significantly associated with os compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72–1.10), p=0.27). other factors associated with poor os were eastern cooperative oncology group (ecog)-performance status (ps) ⩾1, gleason score ⩾8, liver metastasis, high psa, hypoalbuminemia and elevated lactate dehydrogenase (ldh). grade ⩾3 therapy-related toxicities were significantly increased with p plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03–2.13), p=0.034). other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ecog-ps ⩾1, hypoalbuminemia and elevated ldh. fatigue, asthenia, anorexia and pain were not different based on p administration.conclusions:p plus placebo was associated with higher grade ⩾3 toxicities but not extension of os compared with placebo alone in men with mcrpc who received prior docetaxel. except for the use of p with abiraterone to alleviate toxicities, the use of p should be questioned given its association with toxicities and resistance.