Department of Medicine, University of Washington School of Medicine, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Urol Oncol. 2011 Nov-Dec;29(6 Suppl):S1-8. doi: 10.1016/j.urolonc.2011.08.013.
Most men with recurrent prostate cancer (CaP) initially respond to androgen deprivation therapy but eventually develop metastatic castration-resistant prostate cancer (CRPC). Over the last decade, new therapeutic targets have been identified in CRPC and several new drugs have reached advanced stages of clinical development. In 2010, the Food and Drug Administration (FDA) approved sipuleucel-T and cabazitaxel, and in 2011, abiraterone for patients with metastatic CRPC based on phase 3 trials showing improved survival. Although not yet available for clinical use, a press release in June 2011 announced that radium 223 also demonstrated a survival advantage in men with metastatic CRPC. Emerging therapies in advanced stages of clinical development in CRPC include the hormonal therapies MDV3100 and TAK 700, and the immunotherapy ipilimumab. Results are also pending on phase 3 studies comparing docetaxel plus prednisone with docetaxel given with the novel agents aflibercept, dasatinib, lenalidomide, and custirsen. In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. While the addition of these new treatment options is a great advance for men with metastatic CRPC, there are many new questions arising regarding sequencing of these treatments with each other, with previously existing therapies, and with the emerging agents now in clinical trials. Furthermore, there are concerns that on-going phase 3 trials may be contaminated if patients go off study treatment to start 1 of the newly approved agents or take the agent subsequently. These realities make clinical trial design more challenging than ever.
大多数患有复发性前列腺癌（CaP）的男性最初对雄激素剥夺疗法有反应，但最终会发展为转移性去势抵抗性前列腺癌（CRPC）。在过去的十年中，CRPC 中已经确定了新的治疗靶点，并且已经有几种新药进入了临床开发的后期阶段。2010 年，食品和药物管理局（FDA）批准了 sipuleucel-T 和 cabazitaxel，2011 年，abiraterone 也被批准用于转移性 CRPC 患者，这是基于 III 期临床试验显示生存得到改善。尽管尚未可供临床使用，但 2011 年 6 月的一份新闻稿宣布镭 223 也在转移性 CRPC 男性中显示出生存优势。在 CRPC 中处于临床开发后期的新兴疗法包括激素疗法 MDV3100 和 TAK 700，以及免疫疗法 ipilimumab。在比较多西他赛加泼尼松与新型药物 aflibercept、dasatinib、lenalidomide 和 custirsen 联合治疗的 III 期研究中也有结果待公布。除了这些新的和新兴的治疗药物外，地舒单抗还被批准用于预防因实体瘤恶性肿瘤导致的骨转移患者的骨骼并发症，为唑来膦酸提供了替代药物。虽然这些新的治疗选择的加入是转移性 CRPC 男性的巨大进步，但对于这些治疗方法彼此之间、与以前存在的治疗方法之间以及现在正在临床试验中的新兴药物之间的治疗顺序，出现了许多新的问题。此外，人们担心如果患者停止研究治疗而开始使用新批准的药物之一或随后使用该药物，正在进行的 III 期试验可能会受到污染。这些现实使得临床试验设计比以往任何时候都更加具有挑战性。
