The efficacy and safety comparison of docetaxel, cabazitaxel, estramustine, and mitoxantrone for castration-resistant prostate cancer: A network meta-analysis

The aim of this study was to compare the efficacy and safety of docetaxel, cabazitaxel, docetaxel + estramustine, mitoxantrone in the management of castration-resistant prostate cancer (CRPC). Electronic databases including PubMed, Cochrance Library and Embase were searched for studies published from when the databases were established to January 1st, 2018. Randomized controlled trials (RCTs) that compared docetaxel + prednisone (DP), cabazitaxel + prednisone (CP), docetaxel + estramustine + prednisone (DEP), and mitoxantrone + cabazitaxel + prednisone (MP) for CRPC treatment were identified. The network meta-analysis was conducted with software R 3.3.2. We analyzed the main outcomes, including the overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) response, tumor response and severe adverse events (AEs). Ranking of the chemotherapeutic agents was based on probabilities of interventions for each of the outcomes that were performed. The consistency of direct and indirect evidence was assessed by node splitting. 10 RCTs, with 3590 patients, were analyzed. The network meta-analysis results revealed that CP significantly increased OS, PFS, PSA response, tumor response, and severe AEs compared to MP. DP showed similar results with CP except for tumor response, where it showed slight inferiority in effectiveness. DEP was associated with clearly improved outcomes in PFS, PSA response and tumor response compared to those of MP, but this was not the case for OS benefit and severe AEs. No significant difference was detected in DP, CP and DEP except for the outcomes of severe AEs. MP was less effective in survival and clinical benefit, but much safer in safety outcomes than other chemotherapy agents. The probabilities of rank plots showed that CP ranked first in OS and tumor response; DEP ranked first in PFS time and PSA response; MP was the best treatment mode for safety. DP and CP survival benefit (OS, PFS) and clinical benefit (PSA response and tumor response) were comparable, as well as their associated AEs. DEP was associated with less survival benefit, similar clinical improvement and more AEs than DP or CP. MP had the lowest survival and clinical benefit but excellent safety than other agents. Based on evidences of current results, we recommended CP as the most suitable chemotherapy agent for CRPC patients, followed by DP, MP as third, and DEP as the last choice. However, considering limitations of our network meta-analysis