a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA.
Expert Opin Investig Drugs. 2019 Mar;28(3):249-259. doi: 10.1080/13543784.2019.1570130. Epub 2019 Jan 28.
The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials.
We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents often used in combination with LHRH agonists. We review these candidates in the specific clinical niche in which they might find utility.
Of all candidate compounds being evaluated in clinical trials, very few will receive FDA approval. Few, if any of the investigational agents discussed here will be used routinely in clinical practice for treating prostate cancer. Recognizing the reasons for the failure of agents to advance to later stage trials is important. Furthermore, a thorough understanding of the mechanisms underlying prostate cancer pathogenesis, including various points in the HGPA and parallel pathways, will help identify potentially actionable targets.
前列腺癌的治疗和管理仍在不断发展;新的药物类别和联合疗法正在开发中,一些正在进行早期临床试验。
我们讨论了用于治疗前列腺癌的研究性激素药物,并主要关注早期试验中的促黄体激素释放激素(LHRH)激动剂。我们研究了靶向激素轴的药物,包括抗雄激素、促性腺激素、雌激素和孕激素以及其他常用于与 LHRH 激动剂联合使用的非激素药物。我们在它们可能具有应用价值的特定临床领域中评估这些候选药物。
在所有正在临床试验中评估的候选化合物中,只有极少数会获得 FDA 批准。如果有任何这里讨论的研究性药物,它们也很少会在临床上常规用于治疗前列腺癌。认识到药物未能进入后期试验的原因很重要。此外,深入了解前列腺癌发病机制的机制,包括 HGPA 和并行途径中的各个点,将有助于确定潜在的可操作靶点。