Cerbone Linda, Sternberg Cora N, Sengeløv Lisa, Agerbaek Mads, Van Herpen Carla, Marreaud Sandrine, Collette Sandra, Zhang Jianping, Daugaard Gedske
Department of Medical Oncology, San Camillo and Forlanini Hospital, Rome, Italy.
Oncology. 2016;90(1):21-8. doi: 10.1159/000440959. Epub 2015 Oct 16.
BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim was to determine the maximum tolerated dose (MTD) of lapatinib in combination with GC.
A 3 + 3 dose escalation protocol was used with lapatinib at 750, 1,000 and then 1,250 mg. It was dosed daily with gemcitabine (1,000 mg/m2 on days 1, 8 and 15) and cisplatin (70 mg/m2 on day 2) every 28 days. In all, 18 patients with a median age of 63 years (range 50-77) were included; 3/6, 3/5 and 6/7 patients received lapatinib at 750, 1,000 and 1,250 mg, combined with GC, in cohorts 1, 2 and 3, respectively.
No dose-limiting toxicities (DLTs) were observed in cohort 1 or 2 (3 patients each); in cohort 3 (2 × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles.
Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1,250 mg.
背景/目的：拉帕替尼是一种有效的HER1和HER2抑制剂。吉西他滨-顺铂（GC）是晚期/转移性膀胱癌的标准化疗方案。这项I期研究考察了拉帕替尼联合GC用于膀胱癌患者的安全性。主要目的是确定拉帕替尼联合GC的最大耐受剂量（MTD）。
采用3+3剂量递增方案，拉帕替尼剂量分别为750、1000和1250mg。每28天给药一次，拉帕替尼每日服用，吉西他滨（第1、8和15天1000mg/m²）和顺铂（第2天70mg/m²）。总共纳入了18例患者，中位年龄63岁（范围50-77岁）；队列1、2和3中分别有3/6、3/5和6/7例患者接受了750、1000和1250mg拉帕替尼联合GC治疗。
队列1或2（各3例患者）中未观察到剂量限制性毒性（DLT）；在队列3（2×3例患者）中，6例患者中有1例出现DLT（4级，与治疗相关的发热性中性粒细胞减少和肾衰竭）。12例患者接受了6个周期的治疗。
750-1250mg拉帕替尼联合GC似乎安全且耐受性良好。拉帕替尼联合GC用于膀胱癌的MTD为1250mg。
