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Tolerability and safety of EUS-injected adenovirus-mediated double-suicide gene therapy with chemotherapy in locally advanced pancreatic cancer: Phase I Trial.

EUS 注射腺病毒介导的双自杀基因治疗联合化疗治疗局部晚期胰腺癌的耐受性和安全性: I 期试验。

  • 影响因子:2.64
  • DOI:10.1016/j.gie.2020.02.012
  • 作者列表:"Lee JC","Shin DW","Park H","Kim J","Youn Y","Kim JH","Kim J","Hwang JH
  • 发表时间:2020-02-18
Abstract

BACKGROUND AND AIMS:Locally advanced pancreatic cancer (LAPC) is challenging. Here we aimed to evaluate the tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP (Ad5-DS), a replication-competent adenovirus-mediated double-suicide gene therapy in combination with gemcitabine in LAPC patients. METHODS:Newly diagnosed LAPC patients were enrolled in this single-center, open label, 3+3 dose-escalation phase I trial (NCT02894944). Ad5-DS was injected into the pancreatic mass with endoscopic ultrasonography-guided fine needles combined with oral 5-fluorocytosine and valganciclovir, and standard dose of intravenous gemcitabine. The doses of Ad5-DS in cohorts 1 to 3 were 1 × 1011, 3 × 1011, and 1 × 1012 vp/mL, respectively. Patients were observed for dose-limiting toxicity (DLT) for 8 weeks after Ad5-DS injection. Toxicity within 12 weeks, tumor response in 12 weeks, disease progression in 6.5 months, and detection of adenoviral DNA particle in 8 weeks were also assessed. RESULTS:Among the 11 enrolled patients, 9 completed the evaluation period and 2 withdrew their consent. No DLT was reported; thus, the maximum tolerated dose (MTD) was not reached. No additional toxicity was reported in 9 to 12 weeks. One patient showed a partial response and 8 showed stable disease at 12 weeks. Two patients showed disease progression at 6.5 months (median progression-free survival, 11.4 months). At 8 weeks, serum adenoviral DNA particles were detected in 4 patients (median, 55 days). CONCLUSION:Combination of intratumoral Ad5-DS and gemcitabine is safe and well-tolerated in patients with locally advanced pancreatic cancer. This warrants further investigation in a larger clinical trial.

摘要

背景和目的: 局部晚期胰腺癌 (LAPC) 具有挑战性。在这里,我们旨在评估 Ad5-yCD/mutTK (SR39) rep-ADP (Ad5-DS) 的耐受性和安全性, 一种复制活性腺病毒介导的双自杀基因治疗与吉西他滨联合治疗 LAPC 患者。 方法: 新诊断的 LAPC 患者入选本单中心、开放标签、 3 + 3 剂量递增 I 期试验 (NCT02894944)。采用超声内镜引导下细针联合口服 5-氟胞嘧啶和 lovir 更昔洛韦及标准剂量吉西他滨静脉注射 Ad5-DS。队列 1 ~ 3 中 Ad5-DS 的剂量分别为 1 × 1011 、 3 × 1011 和 1 × 1012 vp/mL。观察患者注射 Ad5-DS 后 8 周的剂量限制性毒性 (DLT)。12 周内毒性,12 周肿瘤反应,6.5 个月疾病进展,8 周检测腺病毒 DNA 颗粒也被评估。 结果: 11 例入组患者中,9 例完成评估期,2 例撤回同意。未报告 DLT; 因此,未达到最大耐受剂量 (MTD)。在 9 至 12 周内未报告额外毒性。1 例患者显示部分缓解,8 例患者在 12 周时疾病稳定。2 例患者在 6.5 个月时出现疾病进展 (中位无进展生存期,11.4 个月)。8 周时,检测 4 例患者 (中位数,55 天) 血清腺病毒 DNA 颗粒。 结论: Ad5-DS 联合吉西他滨治疗局部晚期胰腺癌安全、耐受性好。这值得在更大的临床试验中进一步研究。

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影响因子:2.69
发表时间:2020-01-18
DOI:10.1016/j.bbrc.2020.01.048
作者列表:["Li Y","Wang Z","Jin J","Zhu SX","He GQ","Li SH","Wang J","Cai Y"]

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影响因子:2.46
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DOI:10.1097/COC.0000000000000609
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