Immunotherapy and endothelin receptor antagonists for treatment of castration‐resistant prostate cancer

Abstract

Recently, novel therapies of prostate cancer, such as immunotherapy, endothelin receptor antagonists, novel androgen receptor antagonist and novel taxanes, and others have been introduced into clinical practice. This study was performed to summarize these results of immunotherapy and endothelin receptor antagonists in the treatment of castration-resistant prostate cancer (CRPC) and derive a more precise estimation of their effect on future treatment. The PubMed database, references of published trials, and review articles were searched. Two reviewers independently extracted data of these trials. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression-free survival (PFS), or time to disease progression (TTP), and relative risk (RR) for the different types of toxicity. In addition, 95% confidence intervals (CIs) give a sense of the precision of the estimate. Nine randomized controlled trials were ultimately identified. The pooled HR showed that immunotherapy could prolong OS significantly in patients with CRPC compared to placebo (HR 5 0.70, 95% CI: 0.58-0.83, p < 0.001). Endothelin receptor antagonists also had modest benefits (HR 5 0.90, 95% CI: 0.82-1.00, p 5 0.046). Nevertheless, there were no significant benefits from both therapies on PFS or TTP. In addition, immunotherapy led to more fatigue, pyrexia, chills, and endothelin receptor antagonists led to more peripheral edema, anemia, and dyspnea. Our article suggested that the very acceptable toxicity and improving OS in patients with CRPC made immunotherapy an attractive option for such patients. However, future studies with thoughtful clinical trial designs are warranted.Prostate cancer (PCa) is the most common malignancy in males in developed countries. In addition, PCa is the second leading cause of cancer-related death in men in developed countries. In 2012, nearly 241,740 new cases are expected to be diagnosed in the USA with 28,170 estimated deaths.

Review of Animal Models of Prostate Cancer Bone Metastasis

“…These experiments revealed that osteoblasts are activated by the canine prostatic tissue through an endothelin-dependent mechanism [34]. The importance of this work is highlighted by the fact that endothelin has become an important target in human prostate cancer metastases in the last five years [35][36][37][38][39]. This particular model has the advantage of providing an easily manipulated system for investigating prostate-specific mechanisms of new bone formation.…”

MiR-5195-3p Functions as a Tumor Suppressor in Prostate Cancer via Targeting CCNL1

“…There are more than 220,000 estimated new cases of PCa and over 30,000 men die from this disease per year in the United States [3]. Despite great improvement in outcomes of PCa with early-stage by early prostatespeci c antigen (PSA) testing, surgical resection and androgen deprivation therapy [4,5], the prognosis is still poor for the advanced patients, especially the emergence of castration-resistant PCa [6]. Therefore, elucidation of the molecular mechanisms underlying the initiation and progression of PCa is urgently needed to establish new therapeutic targets for PCa treatment.…”

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

“…Zibotentan (ZD4054) is an oral and selective ET-A receptor antagonist in development. Atrasentan (ABT-627) is another orally bioavailable selective ET-A receptor antagonist that inhibits ET-1 activity [ 9 ]. Some randomized controlled trials (RCTs) of ET-A receptor antagonists for the treatment of CRPC are currently available, however the results of those studies have been inconsistent.…”

“…Also the efficacy differences between zibotentan and atrasentan have not been compared. A systematic review by Shao N et al[ 9 ] comparing ET-A receptor antagonists to placebo for CRPC suggested ET-A receptor antagonists are an attractive option for such patients. However, only four studies were included in the analysis, and the comparison of ET-A receptor antagonists and docetaxel was not performed.…”