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A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer.

Qi P, Chen M, Zhang LX, Song RX, He ZH, Wang ZP - PLoS ONE (2015)

Bottom Line: The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC.The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.And there were no significant differences between zibotentan and atrasentan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Clinical Laboratory, The Second Hospital of Lanzhou University, Lanzhou 730030, China.

ABSTRACT

Background: Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate cancer (CRPC). Our aim was to conduct a meta-analysis and indirect comparison to assess the efficacy and safety of ET-A receptor antagonists for treatment of CRPC.

Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to November 2014 to identify randomized controlled trials (RCTs) which assessed ET-A receptor antagonists for treatment of CRPC. Meta-analysis was conducted by STATA version 12.0 software.

Results: Eight RCTs were identified, involving 6,065 patients. The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC. The results of ET-A receptor antagonists plus docetaxel versus docetaxel alone were similar. The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.

Conclusions: There were no significant benefits for ET-A receptor antagonists with or without docetaxel in the improvement of PFS, OS, TTP, and overall AEs. And there were no significant differences between zibotentan and atrasentan. Single-agent docetaxel should remain as one of the standard treatments.

No MeSH data available.


Related in: MedlinePlus

The results of direct comparison of zibotentan and atrasentan for progression-free survival.Squares indicate study-specific hazard ratios (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary hazard ratios with its corresponding 95% confidence interval.
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pone.0133803.g004: The results of direct comparison of zibotentan and atrasentan for progression-free survival.Squares indicate study-specific hazard ratios (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary hazard ratios with its corresponding 95% confidence interval.

Mentions: Three studies [12,13,19] reported PFS of ET-A receptor antagonists versus placebo. The results of heterogeneity and meta-analysis are shown in Fig 4. ET-A receptor antagonists did not significantly improve the PFS (HR = 0.95, 95%CI: 0.85–1.06; P = 0.355) compared with placebo. Two studies [15,17] reported PFS of ET-A receptor antagonists plus docetaxel versus docetaxel alone. The heterogeneity between five studies was P = 0.838, I2 = 0.0%. A fixed effect model was used to analyze the results. There were no statistically significant differences for the two groups (HR = 1.01, 95%CI: 0.92–1.11; P = 0.834) in the improvement of PFS (S1 File).


A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer.

Qi P, Chen M, Zhang LX, Song RX, He ZH, Wang ZP - PLoS ONE (2015)

The results of direct comparison of zibotentan and atrasentan for progression-free survival.Squares indicate study-specific hazard ratios (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary hazard ratios with its corresponding 95% confidence interval.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508042&req=5

pone.0133803.g004: The results of direct comparison of zibotentan and atrasentan for progression-free survival.Squares indicate study-specific hazard ratios (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary hazard ratios with its corresponding 95% confidence interval.
Mentions: Three studies [12,13,19] reported PFS of ET-A receptor antagonists versus placebo. The results of heterogeneity and meta-analysis are shown in Fig 4. ET-A receptor antagonists did not significantly improve the PFS (HR = 0.95, 95%CI: 0.85–1.06; P = 0.355) compared with placebo. Two studies [15,17] reported PFS of ET-A receptor antagonists plus docetaxel versus docetaxel alone. The heterogeneity between five studies was P = 0.838, I2 = 0.0%. A fixed effect model was used to analyze the results. There were no statistically significant differences for the two groups (HR = 1.01, 95%CI: 0.92–1.11; P = 0.834) in the improvement of PFS (S1 File).

Bottom Line: The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC.The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.And there were no significant differences between zibotentan and atrasentan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Clinical Laboratory, The Second Hospital of Lanzhou University, Lanzhou 730030, China.

ABSTRACT

Background: Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate cancer (CRPC). Our aim was to conduct a meta-analysis and indirect comparison to assess the efficacy and safety of ET-A receptor antagonists for treatment of CRPC.

Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to November 2014 to identify randomized controlled trials (RCTs) which assessed ET-A receptor antagonists for treatment of CRPC. Meta-analysis was conducted by STATA version 12.0 software.

Results: Eight RCTs were identified, involving 6,065 patients. The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC. The results of ET-A receptor antagonists plus docetaxel versus docetaxel alone were similar. The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.

Conclusions: There were no significant benefits for ET-A receptor antagonists with or without docetaxel in the improvement of PFS, OS, TTP, and overall AEs. And there were no significant differences between zibotentan and atrasentan. Single-agent docetaxel should remain as one of the standard treatments.

No MeSH data available.


Related in: MedlinePlus