Fujimoto Naohiro
Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Int J Urol. 2016 Feb;23(2):114-21. doi: 10.1111/iju.12907. Epub 2015 Aug 27.
Androgen deprivation therapy is the initial treatment for men with advanced prostate cancer. Almost all these patients eventually develop progressive castration-resistant prostate cancer despite an initial favorable response. Docetaxel was the first agent to show a survival benefit in patients with castration-resistant prostate cancer. After cancer progression on docetaxel, patients with castration-resistant prostate cancer had few therapeutic options. A better understanding of the mechanisms of resistance to androgen deprivation therapy has led to the development of novel agents with distinct mechanisms of action. Prospective, large-scale clinical trials have shown overall survival benefits with the hormonal agents abiraterone acetate and enzalutamide, the immunotherapeutic agent sipuleucel T, the chemotherapeutic agent cabazitaxel, and bone-targeted Ra-223. Although these agents provided clinical benefit, treatment for castration-resistant prostate cancer remains a major clinical challenge. We recognize many questions, such as methods to select patients for specific treatments, optimal sequencing and drug combinations, and means to overcome drug resistance. There is an urgent need to answer these questions and to establish better treatment strategies. The development of biomarkers that are predictive of treatment results is also required. The present article reviews new castration-resistant prostate cancer treatments, and discusses possible resistant mechanisms as well as potential drug combinations and optimal sequencing.
雄激素剥夺疗法是晚期前列腺癌男性患者的初始治疗方法。几乎所有这些患者尽管最初反应良好，但最终都会发展为去势抵抗性前列腺癌。多西他赛是首个在去势抵抗性前列腺癌患者中显示出生存获益的药物。在多西他赛治疗后癌症进展的情况下，去势抵抗性前列腺癌患者的治疗选择很少。对雄激素剥夺疗法耐药机制的更好理解促使了具有独特作用机制的新型药物的研发。前瞻性大规模临床试验已显示，激素药物醋酸阿比特龙和恩杂鲁胺、免疫治疗药物 sipuleucel T、化疗药物卡巴他赛以及骨靶向药物 Ra-223 可带来总生存获益。尽管这些药物提供了临床益处，但去势抵抗性前列腺癌的治疗仍然是一项重大的临床挑战。我们认识到许多问题，例如为特定治疗选择患者的方法、最佳的用药顺序和药物组合，以及克服耐药性的方法。迫切需要回答这些问题并建立更好的治疗策略。还需要开发能够预测治疗结果的生物标志物。本文综述了去势抵抗性前列腺癌的新治疗方法，并讨论了可能的耐药机制以及潜在的药物组合和最佳用药顺序。
