Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.
Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.
复制标题
DOI：
10.1186/1471-2407-14-148
复制
发表时间：
2014-03-04
期刊：
影响因子：
3.8
通讯作者：
Elias D
中科院分区：
文献类型：
--
作者：
Goéré D;Gras-Chaput N;Aupérin A;Flament C;Mariette C;Glehen O;Zitvogel L;Elias D
尽管进行了术前和/或术后全身化疗，但腹膜是根治性治疗后胃癌复发最常见的部位之一。事实上，胃癌引起的腹膜癌病的预后仍然很差，全身化疗的中位生存期不到一年。虽然结直肠癌腹膜癌的预后随着局部腹腔热腹腔化疗（HIPEC）的发展而发生了变化，但胃癌癌病的生存结果仍然令人失望，5年生存率低于20%。因此，需要在完整的细胞减灭术术后立即开发创新的手术疗法，例如腹膜内免疫疗法。在最近的一项随机研究中，在恶性腹水（尤其是胃癌患者）腹腔内输注卡妥索单抗后获得了临床效果。 Catumaxomab 是一种非人源化嵌合抗体，其特点是具有与三种不同类型细胞结合的独特能力：表达上皮细胞粘附分子 (EpCAM) 的肿瘤细胞、T 淋巴细胞 (CD3) 以及辅助细胞 (Fcγ 受体)。由于腹膜是一个具有免疫功能的器官，并且高达 90% 的胃癌表达 EpCAM，因此在完全切除所有宏观疾病（如结直肠癌癌病治疗中的定义）后腹腔内输注卡妥索单抗可以有效治疗微观残留疾病。这项随机 II 期研究的目的是评估与胃癌同步的局限性癌病完全切除后的 2 年总生存率，然后在 2 个组中每组腹腔内输注不同总剂量的卡妥索单抗。将根据停止规则密切监测围手术期死亡率、发病率和早期手术再干预。除此分析外，还将进行转化研究以确定卡妥索单抗功效的免疫学标记物，并将这些标记物与临床疗效相关联。
The peritoneum is one of the most frequent sites of recurrent gastric carcinoma after curative treatment, despite the administration of pre- and/or postoperative systemic chemotherapy. Indeed, the prognosis of peritoneal carcinomatosis from gastric carcinoma continues to be poor, with a median survival of less than one year with systemic chemotherapy. Whereas the prognosis of peritoneal carcinomatosis from colorectal cancer has changed with the development of locally administered hyperthermic intraperitoneal chemotherapy (HIPEC), survival results following carcinomatosis from gastric cancer remain disappointing, yielding a 5-year survival rate of less than 20%. Innovative surgical therapies such as intraperitoneal immunotherapy therefore need to be developed for the immediate postoperative period after complete cytoreductive surgery. In a recent randomised study, a clinical effect was obtained after intraperitoneal infusion of catumaxomab in patients with malignant ascites, notably from gastric carcinoma. Catumaxomab, a nonhumanized chimeric antibody, is characterized by its unique ability to bind to three different types of cells: tumour cells expressing the epithelial cell adhesion molecule (EpCAM), T lymphocytes (CD3) and also accessory cells (Fcγ receptor). Because the peritoneum is an immunocompetent organ and up to 90% of gastric carcinomas express EpCAM, intraperitoneal infusion of catumaxomab after complete resection of all macroscopic disease (as defined in the treatment of carcinomatosis from colorectal cancer) could therefore efficiently treat microscopic residual disease. The aim of this randomized phase II study is to assess 2-year overall survival after complete resection of limited carcinomatosis synchronous with gastric carcinoma, followed by an intraperitoneal infusion of catumaxomab with different total doses administered in each of the 2 arms. Close monitoring of peri-opertive mortality, morbidity and early surgical re-intervention will be done with stopping rules. Besides this analysis, translational research will be conducted to determine immunological markers of catumaxomab efficacy and to correlate these markers with clinical efficacy.
登录
查看更多内容
影响因子：
11.2
作者：
Jaeger, Michael;Schoberth, Alexandra;Lindhofer, Horst
通讯作者：
Lindhofer, Horst
影响因子：
3.7
作者：
Yang XJ;Huang CQ;Suo T;Mei LJ;Yang GL;Cheng FL;Zhou YF;Xiong B;Yonemura Y;Li Y
通讯作者：
Li Y
影响因子：
3.7
作者：
Glehen, Olivier;Gilly, Francois Noel;Elias, Dominique
通讯作者：
Elias, Dominique
影响因子：
45.3
作者：
Ychou, Marc;Boige, Valerie;Rougier, Philippe
通讯作者：
Rougier, Philippe
影响因子：
3.5
作者：
Shi, Chunmei;Yang, Baoyu;Fan, Nanfeng
通讯作者：
Fan, Nanfeng