A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer.
A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer.
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DOI：
10.1007/s10637-011-9658-9
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发表时间：
2012-06
影响因子：
3.4
通讯作者：
Lenz, H. J.
中科院分区：
文献类型：
--
作者：
El-Khoueiry, A. B.;Ramanathan, R. K.;Yang, D. Y.;Zhang, W.;Shibata, S.;Wright, J. J.;Gandara, D.;Lenz, H. J.
转移性胰腺癌患者的治疗选择有限。 Ras-Raf-MAPK 通路和血管内皮生长因子在胰腺癌发生中的作用为在随机 II 期研究中评估索拉非尼联合或不联合吉西他滨的疗效提供了合理依据。转移性胰腺癌患者被随机分配至单用索拉非尼组（A 组）或索拉非尼联合吉西他滨组（B 组）。由于缺乏客观回应，A 组在中期分析时已停止计提。中位 PFS 和 OS 分别为 2.3 和 4.3 个月。 B 组 37 名患者中有 1 名部分缓解。中位 PFS 和 OS 分别为 2.9 个月和 6.5 个月。 B 组有更多 3 级和 4 级毒性，最常见的是中性粒细胞减少 (17%)、血小板减少 (8%)、碱性磷酸酶升高 (14%)、静脉血栓栓塞 (8%)、腹泻、低钾血症和 ALT 升高 (5%)。核糖核苷酸还原酶、Cox-2、血管内皮生长因子的单核苷酸多态性与接受吉西他滨和索拉非尼治疗的患者的生存期之间存在多种关联。单独索拉非尼或索拉非尼与吉西他滨联合治疗均未显示出治疗转移性胰腺癌的有希望的活性。
Patients with metastatic pancreatic cancer have limited therapeutic options. The role of the Ras-Raf-MAPK pathway and of vascular endothelial growth factor in pancreatic carcinogenesis provided the rational to evaluate the efficacy of sorafenib with or without gemcitabine in a randomized phase II study. Patients with metastatic pancreatic cancer were randomized to sorafenib alone (arm A) or sorafenib with gemcitabine (arm B). Arm A was closed to accrual at interim analysis due to the lack of objective response. Median PFS and OS were 2.3 and 4.3 months respectively. There was one partial response among the 37 patients in arm B. Median PFS and OS were 2.9 and 6.5 months respectively. There were more grade 3 and 4 toxicities in arm B with the most common being neutropenia (17%), thrombocytopenia (8%), alkaline phosphatase elevation (14%), venous thromboembolism (8%), diarrhea, hypokalemia and ALT elevation (5%) each. Several associations were noted between single nucleotide polymorphisms in ribonucleotide reductase, Cox-2, vascular endothelial growth factor and survival in patients treated with gemcitabine and sorafenib. Neither sorafenib alone or sorafenib in combination with gemcitabine manifested promising activity in metastatic pancreatic cancer.
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5.3
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