HER2/neu May Not Be an Interesting Target in Biliary Cancers: Results of an Early Phase II Study with Lapatinib
HER2/neu May Not Be an Interesting Target in Biliary Cancers: Results of an Early Phase II Study with Lapatinib
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DOI：
10.1159/000336488
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发表时间：
2012-01-01
期刊：
影响因子：
3.5
通讯作者：
Bekaii-Saab, Tanios
中科院分区：
文献类型：
--
作者：
Peck, Joshua;Wei, Lai;Bekaii-Saab, Tanios
目的：胆道癌（BCs）对化疗反应较差。拉帕替尼是表皮生长因子受体（EGFR）和HER 2/neu的双重抑制剂，两者均参与胆管癌的发生。本试验旨在确定拉帕替尼在BC中的安全性和疗效。方法：采用Fleming II期设计，单期25例患者。拉帕替尼的剂量为1，500 mg/天，口服，28天为一个周期。分析肿瘤和血液标本的HER 2/neu和EGFR表达。结果：9例BC患者入组本研究。研究因无效而提前终止。最常见的毒副反应为恶心、乏力（78%）和腹泻（67%）。未观察到任何反应。在8例可评价患者中，4例（50%）病情稳定。中位无进展生存期为2.6个月（95% CI 1.6-4.4），中位总生存期为5.1个月（95% CI 2.0-16.5）。未发现EGFR（外显子18-21）或HER 2/neu的体细胞突变，也未发现HER 2过表达的证据。结论：拉帕替尼耐受性良好，但作为单一药物治疗BC患者未能显示出活性。尽管患者人群较小，但我们的研究与先前的发现一致，表明靶向HER 2/neu似乎不是BC的有效疗法。
Purpose: Biliary cancers (BCs) respond poorly to chemotherapy. Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, both implicated in cholan-giocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in BC. Methods: A Fleming phase II design with a single stage of 25 patients was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/neu and EGFR. Results: Nine patients with BC enrolled in this study. The study was terminated early because of futility. The most common toxicities were nausea and fatigue (78%) and diarrhea (67%). No responses were observed. Of 8 evaluable patients, 4 (50%) had stable disease. Median progression-free survival was 2.6 months (95% CI 1.6-4.4) and median overall survival was 5.1 months (95% CI 2.0-16.5). No somatic mutations in EGFR (exons 18-21) or HER2/neu were found. We did not find evidence of HER2 overexpression. Conclusions: Lapatinib is well tolerated but failed to show activity as a single agent in treating patients with BC. Despite the small patient population, our study is consistent with previous findings, suggesting that targeting HER2/neu does not appear to be an effective therapy for BC.