Abstract
Background 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.Methods Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m2 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).ResultsThe 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.ConclusionsIn 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.
Highlights
Pancreatic cancer (PC) is the eighth leading cause of cancer-related mortality worldwide [1], and the majority of patients do not have curable disease
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
The proportion of patients with a neutrophil-to-lymphocyte ratio (NLR) of >4.0, which was reported to be a prognostic factor in advanced PC [10], was higher in the GZ 240 mg group than in the other groups (Table 1)
Summary
Pancreatic cancer (PC) is the eighth leading cause of cancer-related mortality worldwide [1], and the majority of patients do not have curable disease. The use of FOLFIRINOX is limited to patients in good medical condition because of high toxicity [2]. Gemcitabine plus nab-paclitaxel is another treatment option for patients in fair medical condition [3]. 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. Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, 1‐30 Fujigaoka, Aoba‐ku, Yokohama, Kanagawa 227‐8501, Japan. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5‐1‐1, Tsukiji, Chuo‐ku, Tokyo 104‐0045, Japan. Cancer Chemother Pharmacol (2017) 80:307–315 trials with other agents such as gemcitabine plus nab-paclitaxel might be beneficial. Keywords Clinical trial · Phase II · Pancreatic cancer · Metastatic · Gemcitabine · Cholecystokinin Electronic supplementary material The online version of this article (doi:10.1007/s00280-017-3351-4) contains supplementary material, which is available to authorized users.
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