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



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.



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.



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.
University of Alabama at Birmingham, Birmingham, AL, USA.
G
G
Sonpavde
McMaster University, Hamilton, Ontario, Canada.
G R
GR
Pond
Kantonsspital St Gallen, St Gallen, Switzerland.
A J
AJ
Templeton
Mayo Clinic, Rochester, MN, USA.
E D
ED
Kwon
The Institute of Cancer Research, London, UK.
J S
JS
De Bono
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D011241:Prednisone