Brand Timothy C, Tolcher Anthony W
Department of Urology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
J Urol. 2006 Dec;176(6 Pt 2):S76-80; discussion S81-2. doi: 10.1016/j.juro.2006.06.080.
We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features.
Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available.
A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied.
Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.
我们回顾了转移性前列腺癌某些新型药物的初步研究结果，并讨论了这些药物对早期疾病（如具有高风险特征的生化复发前列腺癌）的潜在益处。
通过PubMed检索、会议论文集以及未发表的专有信息（如有），获取并回顾了有关某些研究性免疫疗法以及内皮素A受体拮抗剂和生存素抑制剂的现有数据。
大量有前景的药物正处于不同的研发阶段。内皮素A受体拮抗剂阿曲生坦已报道了III期研究结果。几种免疫疗法目前正处于II/III期试验，即粒细胞巨噬细胞集落刺激因子转导的肿瘤细胞疫苗GVAX、负载前列腺酸性磷酸酶的树突状细胞疫苗Provenge以及表达前列腺特异性抗原的痘苗病毒疫苗PROSTVAC-VF。另一种免疫疗法，前列腺特异性膜抗原免疫偶联物MLN2704（千年制药公司，马萨诸塞州剑桥），正处于I/II期研究。生存素的首批临床抑制剂正处于I期早期研究。这些药物中的几种，包括阿曲生坦，在其研究的晚期疾病环境中已显示出具有统计学意义但适度的效果。
这些新型疗法的临床试验设计面临特殊挑战，因为这些药物大多可能诱导疾病稳定而非疾病消退。如果仅在预期寿命以月计算的晚期、经过大量预处理的男性患者中研究这些细胞生长抑制剂，存在假阴性结果以及无法识别潜在有效药物的风险。我们提倡将高危前列腺癌男性患者尽早转诊并纳入临床试验。
