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

• Published in: Prostate cancer and prostatic diseases Vol. 20; no. 1; pp. 67 - 71
• Main Authors: Sonpavde, G, Pond, G R, Templeton, A J, Kwon, E D, De Bono, J S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2017; Nature Publishing Group
• Subjects: 631/67; Aged; Analysis; Anorexia; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Asthenia; Biomedical and Life Sciences; Biomedicine; Cancer metastasis; Cancer Research; Care and treatment; Castration; Clinical trials; Clinical Trials, Phase III as Topic; Confidence intervals; Corticosteroids; Dosage and administration; Humans; Impact analysis; Ipilimumab; Kaplan-Meier Estimate; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Liver cancer; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; original-article; Pain; Patient outcomes; Placebos; Prednisone; Prednisone - administration & dosage; Prednisone - adverse effects; Prognosis; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - mortality; Prostatic Neoplasms, Castration-Resistant - pathology; Regression analysis; Regression models; Risk factors; Statistical analysis; Toxicity; Treatment Outcome
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/pcan.2016.44

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.