Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan
Department of Medical Oncology, Nursing Home 'La Maddalena', Palermo.
Ann Oncol. 2015 Mar;26(3):542-7. doi: 10.1093/annonc/mdu576. Epub 2014 Dec 23.
The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC.
Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes.
A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm).
Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs.
NCT00753675.
由于关于最佳治疗方法的有限数据，胆道癌（BTC）的治疗较为复杂。本项 II 期多中心研究评估了与 vandetanib 联合吉西他滨或安慰剂相比，vandetanib 单药治疗在晚期 BTC 患者中的疗效和耐受性。
患者以 1：1：1 的比例随机分配至 3 个治疗组：vandetanib 300mg 单药治疗（V 组）、vandetanib 100mg 联合吉西他滨（V/G 组）、吉西他滨联合安慰剂（G/P 组）。vandetanib（300mg 或 100mg）或安慰剂每日单次口服给药。吉西他滨 1000mg/m2 于每个 21 天周期的第 1 天及第 8 天静脉输注。主要终点为无进展生存期（PFS）。次要终点为：客观缓解率（ORR）、疾病控制率、总生存期、缓解持续时间、功能状态和安全性结果。
共在意大利 19 个中心招募了 173 例患者（平均年龄 63.6 岁）。V、V/G 和 G/P 治疗组的中位（95%置信区间）PFS（天）分别为 105（72-155）、114（91-193）和 148（71-225），各组之间无统计学差异（P = 0.18）。除 ORR 外，各治疗组之间在次要终点方面也无统计学差异，V/G 联合治疗稍优于其他治疗。报告不良事件（AE）的患者比例在三组间相似（V 组为 96.6%，V/G 组为 91.4%，G/P 组为 89.3%）。
vandetanib 治疗未能改善晚期 BTC 患者的 PFS。vandetanib 的安全性无额外 AE 发生，也未加重已知 AE。
NCT00753675。
