转移性去势抵抗性前列腺癌化疗与激素治疗策略

以多西他赛为核心的化疗方案已经成为转移性去势抵抗性前列腺癌（ metastatic castrate－resistant prostate cancer，mCRPC）治疗的一线方案。但在过去的几年中，一些新药的出现改善了患者的总体生存，同时也使优化个体化治疗方案成为可能。已有证据表明阿比特龙、卡巴他赛、镭－223、sipuleucel－T、恩杂鲁胺等与多西他赛一同使去势抵抗性前列腺癌患者生存获益。另外，mCRPC患者对多西他赛一线治疗初始反应良好，出现疾病进展后复治应作为一线治疗的延伸。这些新的治疗手段使mCRPC治疗方案更加复杂化，并且使以往的序贯治疗方案向基于一定规则的新的治疗方式转变。

Sipuleucel-T在晚期前列腺癌免疫治疗中的应用研究

Sipuleucel-T (Provenge(R))为第一个被美国FDA批准的治疗性肿瘤疫苗,是一种自体活性细胞免疫治疗方法,用于无症状或者症状轻微的转移性激素抵抗性前列腺癌患者(mCRPC).因而对Sipuleucel-T的制备、临床应用及新研究进展等方面的了解很重要.

Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

去势抵抗性前列腺癌的发生发展机制及药物治疗新进展

去势抵抗性前列腺癌(CRPC)患者预后极差.CRPC的发生和进展机制极为复杂,迄今尚未被完全阐明,因此治疗策略的选择仍是临床上极具挑战性的问题.近年来,治疗CRPC的新药不断涌现,包括雄激素合成抑制药物(阿比特龙)、雄激素受体(AR)抑制药物(恩杂鲁胺)、免疫治疗剂(sipuleucel-T)、放射剂(镭-223)和化疗药物(卡巴他赛)等.因而,针对CRPC的治疗有了更多选择,系统治疗亦发生了很大变化.简要综述近年来人们对CRPC发生发展机制的新理解和有前途的药物在CRPC治疗中获得的新进展.

首个晚期前列腺癌免疫治疗药物Sipuleucel-T的研究

Sipuleucel-T是一种新型免疫治疗药物的代表,它可以刺激机体的免疫反应来抗击非激素依赖型前列腺癌.Sipuleucel-T是一种自体细胞来源的免疫治疗药,它由自体树突状细胞(DCs)与融合蛋白PA2024在体外共孵化获得,其中PA2024是一种由前列腺酸性磷酸酶(PAP)和粒细胞巨噬细胞集落刺激因子(GM-CSF)构建的融合蛋白(PAP-GM-CSF).尽管Sipuleucel-T缺乏对前列腺癌特异性抗原的免疫反应,但随机Ⅲ期临床试验表明了Sipuleucel-T对无症状的或者症状轻微的激素耐受型前列腺癌患者的总体生存期有重大改善.本文阐述了当前前列腺癌一些治疗方法,同时重点介绍了Sipuleucel-T的制备、作用机制以及临床研究.