A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer
A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer
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DOI：
10.1158/1078-0432.ccr-05-2059
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发表时间：
2006-02-15
影响因子：
11.5
通讯作者：
Dahut, W
中科院分区：
文献类型：
--
作者：
Arlen, PM;Gulley, JL;Dahut, W
目的：多西紫杉醇具有抗雄激素非依赖性前列腺癌的活性，临床前研究表明基于紫杉烷的化疗可以增强疫苗的抗肿瘤反应。本研究的主要目的是确定同时使用多西他赛（与地塞米松）是否对产生疫苗免疫反应有任何影响。次要终点是是否可以安全地使用多西紫杉醇接种疫苗以及治疗方案的临床结果。 实验设计：疫苗接种方案由 (a) 表达前列腺特异性抗原基因 (rV-PSA) 的重组痘苗病毒 (rV) 与 (b) 表达 B7.1 共刺激基因的 rV 混合组成 (rV-B7.1)，和(c)用含有PSA基因(rF-PSA)的重组鸡痘病毒(rF-)连续加强疫苗接种。患者每次接种疫苗时都会接受粒细胞巨噬细胞集落刺激因子。 28 名患有转移性雄激素非依赖性前列腺癌的患者被随机分配接受疫苗和每周多西紫杉醇治疗或单独接受疫苗治疗。仅接受疫苗组的患者在疾病进展时被允许交叉接受仅接受多西紫杉醇治疗。 ELISPOT 测定用于监测 PSA 特异性 T 细胞的免疫反应。结果：治疗 3 个月后，双臂中这些 PSA 前体 T 细胞的中位数增加了 3.33 倍。此外，疫苗接种后还检测到对其他前列腺癌相关肿瘤抗原的免疫反应。 11 名仅接种疫苗后病情进展的患者在病情进展时转而接受多西紫杉醇治疗。接受疫苗后多西紫杉醇的中位无进展生存期为 6.1 个月，而历史对照中使用相同方案的中位无进展生存期为 3.7 个月。结论：这是第一个临床试验，表明多西紫杉醇可以安全地与免疫疗法一起给药，而不抑制疫苗特异性 T 细胞反应。此外，与单独接受多西紫杉醇的历史对照患者相比，先前接种过抗癌疫苗的患者对多西紫杉醇的反应可能更长。需要更大规模的前瞻性临床研究来验证这些发现。
Purpose: Docetaxel has activity against androgen-independent prostate cancer and preclinical studies have shown that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary end points were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen.Experimental Design: The vaccination regimen was composed of (a) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (b) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (c) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF-PSA). Patients received granulocyte macrophage colony-stimulating factor with each vaccination. Twenty-eight patients with metastatic androgen-independent prostate cancer were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells.Results: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer-associated tumor antigens were also detected postvaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median progression-free survival on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control.Conclusion: This is the first clinical trial to show that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings.