S-1加顺铂联合肽疫苗治疗晚期胃癌患者的人血管内皮生长因子受体1和2的I / II期研究。,International Journal of Oncology

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S-1加顺铂联合肽疫苗治疗晚期胃癌患者的人血管内皮生长因子受体1和2的I / II期研究。
International Journal of Oncology ( IF 4.5 ) Pub Date : 2012-07-31 , DOI: 10.3892/ijo.2012.1573
Toru Masuzawa ₁ , Yoshiyuki Fujiwara , Kaoru Okada , Ayumu Nakamura , Shuji Takiguchi , Kiyokazu Nakajima , Hiroshi Miyata , Makoto Yamasaki , Yukinori Kurokawa , Ryuji Osawa , Kazuyoshi Takeda , Koji Yoshida , Takuya Tsunoda , Yusuke Nakamura , Masaki Mori , Yuichiro Doki

Affiliation

这项研究的目的是评估人白细胞抗原（HLA）-A24限制性人血管内皮生长因子受体1（VEGFR1）-1084和VEGFR2-169联合化学疗法在晚期胃癌患者中的安全性和有效性。对患有晚期或复发性胃腺癌的HLA-A 2402阳性患者接种VEGFR1-1084和VEGFR2-169联合S-1和顺铂。该研究包括22位患者（中位年龄60.5岁），他们接受了至少一个周期的联合治疗。除了6名患者注射部位的炎症反应外，未观察到疫苗治疗引起的严重不良反应。在两个疗程的联合治疗后，有12位患者（55％）表现出部分缓解，其中10位病情稳定。在两个周期后，疾病控制率（部分反应和稳定疾病）为100％。平均进展时间为9.6个月，平均总生存时间为14.2个月。在22例患者中有18例（82％）诱导了VEGFR1-1084特异性细胞毒性T淋巴细胞（CTL）反应，在22例患者中18例（82％）诱导了VEGFR2-169特异性CTL反应。显示CTL对VEGFR2-169肽有反应的患者的预后要好于不存在CTL的患者，如总生存期（OS）和进展时间（TTP）所证明（OS，p = 0.028，TTP，p = 0.006）。联合疗法在晚期或复发性胃癌中耐受性良好且非常有效。即使在化学疗法下，也经常诱导出两种肽的实质性特异的CTL。因此，

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Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer.

The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A 2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.

更新日期：2019-11-01

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