Safety and Efficacy of the Specific Endothelin-A Receptor Antagonist ZD4054 in Patients with Hormone-Resistant Prostate Cancer and Bone Metastases Who Were Pain Free or Mildly Symptomatic: A Double-Blind, Placebo-Controlled, Randomised, Phase 2 Trial

摘要

Background: The endothelin-A receptor (ETAR) has been implicated in the progression of prostate cancer.Objectives: To investigate the safety and efficacy of the specific ETAR antagonist ZD4054 in patients with metastatic hormone-resistant prostate cancer (HRPC). Design, setting, and participants: Double-blind, placebo-controlled, randomised, parallel-group, multicentre, phase 2 trial in patients attending cancer centres with HRPC and bone metastases who were pain free or mildly symptomatic for pain.Intervention: Patients were randomised to receive once-daily oral tablets of ZD4054 10 mg, or ZD4054 15 mg, or placebo.Measurements: The primary end point was time to progression, defined as clinical progression, requirement for opiate analgesia, objective progression of soft-tissue metastases, or death in the absence of progression. Secondary end points included overall survival, time to prostate-specific antigen (PSA) progression, and safety. Statistical significance was preset at 20%.