Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Oncology. 2011;81(1):50-4. doi: 10.1159/000330769. Epub 2011 Sep 15.
Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and RET (REarranged during Transfection) signaling. The primary objective of this open-label phase I trial was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of vandetanib in combination with gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma (PAC).
Patients received vandetanib (100 or 300 mg/day) plus gemcitabine (1,000 mg/m(2) i.v. on days 1, 8 and 15 per 28-day cycle) until disease progression, unacceptable toxicity or withdrawal of patient consent. The MTD was determined by the assessment of dose-limiting toxicity (DLT) during the first 28 days of treatment.
Fifteen patients were treated. No DLTs occurred in the first cohort of vandetanib 100 mg (n = 3) and recruitment continued at the 300-mg dose level. At the 300-mg dose, 3 out of 12 patients (including 2 in the expansion cohort) experienced DLTs (aphasia, elevated liver enzymes and neutropenia; all of them grade 3), thus exceeding the MTD. No objective responses were observed, with stable disease being the best response in 78% of evaluable patients.
Vandetanib 100 mg/day is the RD in combination with gemcitabine in the treatment of patients with advanced PAC.
凡德他尼是一种血管内皮生长因子受体、表皮生长因子受体和 RET（转染重排）信号的口服抑制剂。这项开放标签的 I 期临床试验的主要目的是确定凡德他尼联合吉西他滨治疗不可切除的局部晚期或转移性胰腺腺癌（PAC）患者的最大耐受剂量（MTD）和推荐剂量（RD）。
患者接受凡德他尼（100 或 300mg/天）加吉西他滨（1000mg/m2静脉注射，每 28 天周期的第 1、8 和 15 天），直至疾病进展、无法耐受的毒性或患者撤回同意。MTD 通过治疗的前 28 天评估剂量限制性毒性（DLT）来确定。
15 名患者接受了治疗。凡德他尼 100mg 组的第一个队列中没有发生 DLT（n=3），并且在 300mg 剂量水平继续招募。在 300mg 剂量下，12 名患者中有 3 名（包括扩展队列中的 2 名）出现 DLT（失语症、肝酶升高和中性粒细胞减少；均为 3 级），因此超过了 MTD。没有观察到客观反应，78%的可评估患者的最佳反应是疾病稳定。
凡德他尼 100mg/天联合吉西他滨是治疗晚期 PAC 患者的 RD。
