Ueno Makoto, Li Chung Pin, Ikeda Masafumi, Ishii Hiroshi, Mizuno Nobumasa, Yamaguchi Taketo, Ioka Tatsuya, Oh Do Youn, Ichikawa Wataru, Okusaka Takuji, Matsuyama Yutaka, Arai Daichi, Chen Li Tzong, Park Young Suk, Furuse Junji
Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama-shi, Kanagawa, 241-8515, Japan.
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shin-Pai Road, Taipei, 11217, Taiwan.
Cancer Chemother Pharmacol. 2017 Aug;80(2):307-315. doi: 10.1007/s00280-017-3351-4. Epub 2017 Jun 20.
We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer.
Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m gemcitabine for each cycle and Z-360 tablets of 60 mg (GZ 60 mg group), 120, 240 mg or placebo tablets (Gem group) orally twice daily. The primary endpoint was overall survival (OS).
The median OS was 1.3 months longer in the GZ 60 mg group compared with the Gem group (8.5 vs. 7.2 months) and the risk of death was reduced by 19% compared with the Gem group, although there were no statistically significant differences. The study treatments were well tolerated.
In this Phase II study, no statistically significant differences between the GZ groups and Gem group were detected in any analysis. However, Z-360 in dose of 60 mg tends to improve OS in patients with metastatic pancreatic cancer with low toxic effect. Further exploratory trials with other agents such as gemcitabine plus nab-paclitaxel might be beneficial.
我们研究了60毫克、120毫克或240毫克Z-360（一种高效的胆囊收缩素2受体选择性拮抗剂）与吉西他滨联合应用于转移性胰腺癌患者的疗效和安全性。
患者按1:1:1:1的比例随机分配至四个治疗组之一。患者每个周期接受1000毫克/平方米的吉西他滨，Z-360片60毫克（GZ 60毫克组）、120毫克、240毫克或安慰剂片（吉西他滨组），每日口服两次。主要终点为总生存期（OS）。
GZ 60毫克组的中位总生存期比吉西他滨组长1.3个月（8.5个月对7.2个月），与吉西他滨组相比死亡风险降低了19%，尽管无统计学显著差异。研究治疗耐受性良好。
在这项II期研究中，GZ组和吉西他滨组在任何分析中均未检测到统计学显著差异。然而，60毫克剂量的Z-360倾向于改善转移性胰腺癌患者的总生存期且毒性作用低。使用其他药物如吉西他滨加纳米白蛋白结合型紫杉醇进行进一步的探索性试验可能有益。
