Sipuleucel-T: A vaccine for metastatic, asymptomatic, androgen-independent prostate cancer
Sipuleucel-T: A vaccine for metastatic, asymptomatic, androgen-independent prostate cancer
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DOI：
10.1345/aph.1k429
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Kockler, Denise R.
中科院分区：
文献类型：
--
作者：
Patel, Punam H.;Kockler, Denise R.
目的：应用计算机检索英文文献MEDLINE(1966-2007-09)和Cochrane数据库(2007，第3期)，检索词为siPuleucel-T、APC8015和前列腺癌疫苗，并对其设计、有效性、安全性、剂量、治疗和药物经济学等方面进行综述。从选定文章的书目和新闻稿中确定其他数据来源。研究选择和数据提炼：所有已发表的关于雄激素非依赖性前列腺癌(APIC)的唾液酸T的人类研究的文章或摘要都被纳入。制造商网站、食品和药物管理局(FDA)文件和临床试验注册被用来获得正在进行的临床试验的信息。DATA综合：APIC是一种不治之症，中位存活率为18-20个月。以多西紫杉醇为基础的化疗是目前FDA批准的唯一一种对AIPC有生存益处(2.4mo)的治疗方法。SiPuleucel-T是一种正在研究中的新的主动细胞免疫疗法，用于治疗转移性、无症状的AIPC。在临床试验中，疾病进展时间的主要终点没有得到满足；然而，一项力量不足的数据分析表明，与安慰剂相比，siPuleucel-T延长生存期的中位数为4.5个月。西普鲁切尔-T的耐受性相对较好，尽管可能会增加脑血管事件的风险。2007年5月，FDA没有批准siPuleucel-T的生物制品许可证申请，因为没有达到3期试验的主要终点。然而，一旦正在进行的第三阶段试验IMPACT的临时生存结果确定后，FDA将重新考虑其批准。这些数据预计将在2008年第四季度公布。结论：转移性AIPC是一种不治之症，目前治疗选择有限。SiPuleucel-T的批准取决于IMPACT试验的结果。如果显示存活率提高，西普鲁尔-T可能成为第一个被批准的用于治疗转移性、无症状AIPC的主动细胞免疫疗法。
OBJECTIVE: To review the design, the efficacy, safety, dosing, therapeutic, and pharma-coeconomic considerations of sipuleucel-T, an investigational, autologous, dendritic cell-based prostate cancer vaccine.DATA SOURCES: English-language literature searches of MEDLINE (1966-September 2007) and the Cochrane Database (2007, Issue 3) were performed using the terms sipuleucel-T, APC8015, and prostate cancer vaccine. Other data sources were identified from bibliographies of selected articles and from press releases.STUDY SELECTION AND DATA EXTRACTION: All published articles or abstracts on human studies of sipuleucel-T for androgen-independent prostate cancer (APIC) were reviewed for inclusion. Manufacturer Web sites, Food and Drug Administration (FDA) documents, and the clinical trials registry were used to obtain information regarding ongoing clinical trials.DATA SYNTHESIS: APIC is an incurable disease with a median survival rate of 18-20 months. Docetaxel-based chemotherapy is currently the only FDA-approved treatment for AIPC with a survival benefit (2.4 mo). Sipuleucel-T is a novel active cellular immunotherapy under investigation for the treatment of metastatic, asymptomatic AIPC. In clinical trials, the primary endpoint of time to disease progression was not met; however, an underpowered analysis of data suggests that sipuleucel-T prolongs survival by a median of 4.5 months compared with placebo. Sipuleucel-T has been relatively well tolerated, although a possible increased risk of cerebrovascular events may exist. In May 2007, the FDA did not approve the biologics license application for sipuleucel-T since the primary endpoint of the Phase 3 trials was not met. However, its approval will be reconsidered by the FDA once interim survival results from an ongoing Phase 3 trials, IMPACT, are determined. These data are anticipated to be released in the fourth quarter of 2008.CONCLUSIONS: Metastatic AIPC is an incurable disease that currently has limited treatment options. Approval of sipuleucel-T hinges on results from the IMPACT trial. If improved survival is shown, sipuleucel-T may become the first approved active cellular immunotherapy for treating metastatic, asymptomatic AIPC.