UCL, London, UK.
Eur J Cancer. 2010 Feb;46(3):526-33. doi: 10.1016/j.ejca.2009.11.004. Epub 2009 Dec 14.
To evaluate the combination of the gastrin antagonist Z-360 and gemcitabine for advanced pancreatic cancer.
Previously untreated patients with PC were randomly allocated to Z-360 120 mg, 240 mg or placebo. Z-360/placebo was given on day -3 and gemcitabine 1000 mg/m(2) commenced on day 1 followed by Z-360 on day 2. Thereafter Z-360/placebo was given twice daily concurrently with standard dose of gemcitabine. Pharmacokinetics for both drugs was measured alone and in combination. Toxicity, response and quality of life were also recorded.
Thirty-three patients with a median age of 62 years were randomised of which six had locally advanced disease and 26 had metastatic disease. Analysis of the area under the plasma concentration versus time curve (AUC), the maximum observed concentration (Cmax(obs)) and the time of the maximum observed concentration (Tmax(obs)) for Z-360, gemcitabine and 2,2-difluorodeoxyuridine (dFdU), could not exclude an effect on the systemic exposure to Z-360, gemcitabine and dFdU when co-administration of Z-360 and gemcitabine was compared with single agent administration. The most commonly reported adverse events were nausea, abdominal pain, vomiting and fatigue. At the end of the study, 62.5%, 25% and 60% had stable disease in the 120 mg, 240 mg and placebo group, respectively. A higher proportion of patients in Z-360 groups reported improvement in pain.
Z-360 is safe and well tolerated when combined with gemcitabine. A Phase III trial is needed to determine whether the combination of Z-360 and gemcitabine is superior to gemcitabine alone in advanced PC.
评估胃泌素拮抗剂 Z-360 与吉西他滨联合用于晚期胰腺癌。
先前未经治疗的 PC 患者被随机分配到 Z-360 120mg、240mg 或安慰剂组。Z-360/安慰剂于-3 天给予，吉西他滨 1000mg/m(2)于 1 天开始，随后于 2 天给予 Z-360。此后，Z-360/安慰剂与标准剂量吉西他滨同时每日给药 2 次。单独和联合测量了两种药物的药代动力学。还记录了毒性、反应和生活质量。
33 名中位年龄为 62 岁的患者被随机分组，其中 6 名患者患有局部晚期疾病，26 名患者患有转移性疾病。Z-360、吉西他滨和 2,2-二氟脱氧尿苷（dFdU）的血浆浓度-时间曲线下面积（AUC）、最大观测浓度（Cmax(obs)）和最大观测浓度时间（Tmax(obs)）的分析不能排除当 Z-360 与吉西他滨联合给药时对 Z-360、吉西他滨和 dFdU 的全身暴露的影响与单药给药相比。最常见的不良反应是恶心、腹痛、呕吐和疲劳。在研究结束时，120mg、240mg 和安慰剂组分别有 62.5%、25%和 60%的患者疾病稳定。Z-360 组有更多的患者报告疼痛改善。
Z-360 与吉西他滨联合使用是安全且耐受良好的。需要进行 III 期试验以确定 Z-360 与吉西他滨联合治疗是否优于吉西他滨单药治疗晚期 PC。
