Prostate cancer remains the second leading cause of
cancer death in men due to inefficiency of
androgen deprivation
therapy or
androgen blockade.
Endothelins (ETs) and the two
endothelin receptor family members A and B (ETA and ETB) are known to play important roles in the progression of many
malignancies, including
prostate cancer. However, phase III clinical studies did not reach a unanimous conclusion regarding ETA receptor antagonists in
prostate cancer treatment. Here, we provide a meta-analysis of clinical studies using ETA receptor antagonists to treat
prostate cancer, especially the
hormone refractory
prostate cancer (HRPC). Data were extracted from nine studies that used
Zibotentan or
Atrasentan, two selective ETA receptor antagonists, to treat
prostate cancer and meet the selection criteria. The results indicated that the overall survival (OS) and the progression-free survival (PFS) of patients treated with
Zibotentan did not show significant difference with the patients treated with placebo (pooled hazard ratio (HR) for OS, 0.86, 95% CI 0.70-1.06; pooled HR for PFS, 0.98, 95% CI 0.91-1.06). No statistically significant difference was detected either as to the OS and PFS of patients between the
Atrasentan treated group and the group treated with placebo (pooled HR for OS, 0.99, 95% CI 0.90-1.08; pooled HR for PFS, 0.94, 95% CI 0.86-1.02). Notably, the level of
prostate-specific antigen (PSA) and the incidence of bone
pain were significantly lower in the
Atrasentan treated patients compared to the controls (pooled HR for time of PSA progression, 0.87, 95% CI 0.78-0.97; and pooled relative risk (RR) for bone
pain, 0.68, 95% CI 0.48-0.97). In addition, increasing of PSA and bone
alkaline phosphatase (BALP) were significantly delayed with
Atrasentan treatment (P<0.05). Together, these data suggest that
Atrasentan has an effect on
cancer-related bone
pain and skeletal-events in patients with
prostate cancer.