Slovin Susan
Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Clin Adv Hematol Oncol. 2012 Feb;10(2):90-100.
In prostate cancer, there is considerable evidence that tumors promote immune tolerance starting early in the disease. By suppressing tumors and activating immune system homeostatic mechanisms, chemotherapy may help overcome this tumor-induced immune tolerance. As such, chemotherapy may therefore support improved results from novel immune-modulating therapies. Prostate cancer is particularly suited for active immunotherapy because prostate tumor cells express a number of distinctive surface antigens. Sipuleucel-T, which has recently been approved in the United States, is an active immunotherapy that triggers T-cell responses against prostate cancer. An exploratory analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, VITAL-2, a phase III trial investigating a prostate cancer therapeutic vaccine plus concurrent docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed lower overall survival with the vaccine regimen. This trial highlights major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy. Patient characteristics, prostate cancer disease stage, and treatment history also may influence the response to combined therapy. Advances in biomarker validation and trial design are needed to efficiently investigate these issues.
在前列腺癌中，有大量证据表明肿瘤在疾病早期就开始促进免疫耐受。通过抑制肿瘤并激活免疫系统的稳态机制，化疗可能有助于克服这种肿瘤诱导的免疫耐受。因此，化疗可能会支持新型免疫调节疗法取得更好的效果。前列腺癌特别适合主动免疫疗法，因为前列腺肿瘤细胞表达多种独特的表面抗原。最近在美国获批的西妥昔单抗是一种主动免疫疗法，可触发针对前列腺癌的T细胞反应。一项对III期试验参与者的探索性分析发现，在接受西妥昔单抗治疗数月后再接受多西他赛治疗，可带来显著生存获益。然而，VITAL-2（一项在晚期前列腺癌中研究前列腺癌治疗性疫苗加同期多西他赛与标准多西他赛疗法对比的III期试验）观察到疫苗方案组的总生存期较低。该试验凸显了有关化疗相对于主动免疫疗法的最佳选择、剂量和时机的主要未解决问题。患者特征、前列腺癌疾病分期和治疗史也可能影响联合治疗的反应。需要在生物标志物验证和试验设计方面取得进展，以有效地研究这些问题。
