Polotti Charles F, Kim Christopher J, Chuchvara Nadiya, Polotti Alyssa B, Singer Eric A, Elsamra Sammy
a Division of Urology , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.
b Department of Pharmacy Practice and Pharmacy Administration , University of the Sciences, Philadelphia College of Pharmacy , Philadelphia , PA , USA.
Expert Opin Drug Metab Toxicol. 2017 Dec;13(12):1265-1273. doi: 10.1080/17425255.2017.1405934. Epub 2017 Nov 20.
Medical therapy has undergone many changes as our understanding of prostate cancer cell biology has improved. Androgen deprivation therapy (ADT) remains the mainstay of therapy for metastatic disease. Metastatic castrate-resistant prostate cancer (CRPC) is an important concern since we are unable to stop progression with currently available agents. Areas covered: Pharmacologic ADT is the most commonly used treatment for metastatic prostate cancer. Multiple agents are available for both first-line and second-line use: antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, and CYP17 inhibitors. With adoption of these drugs, it is important to consider their pharmacokinetic and pharmacodynamic properties. Many undergo metabolism through cytochrome P450. Levels may be altered with co-administration of drugs acting as enzyme inhibitors or inducers. Understanding mechanism of action, metabolism, and excretion of these drugs allows clinicians to provide the best therapeutic care while minimizing adverse events. Expert opinion: Many men with metastatic prostate cancer will progress to castration resistance. An understanding of resistance mechanisms at the cellular level has revealed new drug targets with hopes of halting or reversing progression of metastatic disease. Second-line agents, traditionally reserved for CRPC, are being studied in metastatic castrate-sensitive prostate cancer, and may offer practice-changing evidence supporting their use.
随着我们对前列腺癌细胞生物学的理解不断深入，医学治疗已经经历了许多变革。雄激素剥夺疗法（ADT）仍然是转移性疾病治疗的主要手段。转移性去势抵抗性前列腺癌（CRPC）是一个重要问题，因为我们目前无法用现有药物阻止其进展。涵盖领域：药物性ADT是转移性前列腺癌最常用的治疗方法。一线和二线治疗都有多种药物可供选择：抗雄激素药物、雌激素、促黄体生成素释放激素激动剂/拮抗剂以及CYP17抑制剂。在使用这些药物时，考虑它们的药代动力学和药效学特性非常重要。许多药物通过细胞色素P450进行代谢。与作为酶抑制剂或诱导剂的药物联合使用时，药物水平可能会改变。了解这些药物的作用机制、代谢和排泄情况，有助于临床医生在尽量减少不良事件的同时提供最佳治疗。专家观点：许多转移性前列腺癌男性患者会发展为去势抵抗。对细胞水平耐药机制的理解揭示了新的药物靶点，有望阻止或逆转转移性疾病的进展。传统上用于CRPC的二线药物正在转移性去势敏感性前列腺癌中进行研究，可能会提供支持其使用的改变临床实践的证据。
