Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma.
Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma.
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腺病毒介导的单纯疱疹病毒胸苷激酶给药可改善复发性高级别胶质瘤的预后
DOI：
10.18632/oncotarget.6737
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发表时间：
2016-01-26
期刊：
影响因子：
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通讯作者：
Li N
中科院分区：
文献类型：
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作者：
Ji N;Weng D;Liu C;Gu Z;Chen S;Guo Y;Fan Z;Wang X;Chen J;Zhao Y;Zhou J;Wang J;Ma D;Li N
这项随机、开放、多中心、II期临床试验旨在评估复制缺陷型腺病毒突变型胸苷激酶（ADV-TK）联合更昔洛韦治疗复发性高级别胶质瘤（HGG）患者的抗肿瘤疗效和安全性。53例复发性HGG患者随机分配接受ADV-TK脑动脉内灌注或常规治疗。主要终点是6个月无进展生存期（PFS-6）。次要终点包括无进展生存期（PFS）、总生存期（OS）、安全性和临床获益。本试验注册于Clinicaltrials.gov，NCT 00870181。ADV-TK组PFS-6为54.5%，中位PFS为29.6周，中位OS为45.4周，与对照组相比，生存期更长。ADV-TK组1年PFS和OS分别为22.7%和44.6%，临床获益为68.2%。ADV-TK组有2例患者存活超过4年，无进展。在胶质母细胞瘤亚组中，ADV-TK组的PFS-6为71.4%，中位PFS为34.9周，中位OS为45.7周，明显优于对照组。ADV-TK组1年PFS和OS分别为35.7%和50.0%。ADV-TK/更昔洛韦基因治疗耐受性良好，未观察到治疗相关的严重不良事件。我们的研究表明，ADV-TK治疗组的PFS-6、PFS和OS显著改善，疗效和安全性似乎与其他报告的用于复发性HGG的治疗相当。因此，ADV-TK基因治疗是复发性HGG的一种有价值的治疗选择。
This randomized, open-label, multicenter, phase II clinical trial was conducted to assess the anti-tumor efficacy and safety of replication-deficient adenovirus mutant thymidine kinase (ADV-TK) in combination with ganciclovir administration in patients with recurrent high-grade glioma (HGG). 53 patients with recurrent HGG were randomly allocated to receive intra-arterial cerebral infusion of ADV-TK or conventional treatments. The primary end point was 6-month progression-free survival (PFS-6). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and clinical benefit. This trial is registered with Clinicaltrials.gov, NCT00870181. In ADV-TK group, PFS-6 was 54.5%, the median PFS was 29.6 weeks, the median OS was 45.4 weeks, and better survivals were achieved when compared with control group. The one-year PFS and OS were 22.7% and 44.6% in ADV-TK group respectively, and clinical benefit was 68.2%. There are 2 patients alive for more than 4 years without progression in ADV-TK group. In the subgroup of glioblastoma received ADV-TK, PFS-6 was 71.4%, median PFS was 34.9 weeks, median OS was 45.7 weeks respectively, much better than those in control group. The one-year PFS and OS were 35.7% and 50.0% in ADV-TK group respectively. ADV-TK/ganciclovir gene therapy was well tolerated, and no treatment-related severe adverse events were noted. Our study demonstrated a notable improvement of PFS-6, PFS and OS in ADV-TK treated group, and the efficacy and safety appear to be comparable to other reported treatments used for recurrent HGG. ADV-TK gene therapy is therefore a valuable therapeutic option for recurrent HGG.