分子靶向药物治疗晚期胆道肿瘤的研究进展

Research advances in molecular targeted therapy for advanced biliary tract cancer

随着胆道肿瘤基础研究的深入,分子靶向治疗成为新的热点。旨在对分子靶向治疗晚期胆道肿瘤的Ⅱ、Ⅲ临床试验作一综述,为临床实践提供新的思路。Ⅱ临床试验中,血管生长因子受体阻滞剂、有丝分裂原活化蛋白激酶阻滞剂没有体现良好的抗肿瘤活性,而表皮生长因子受体抑制剂对晚期胆道肿瘤显示出良好的安全性和有效性。唯一的一项Ⅲ期随机、开放、多中心对照研究表明尼洛替尼联合吉西他滨、奥沙利铂作为晚期胆道肿瘤一线治疗手段未能显著改善患者的总体生存。亚组分析胆管癌能从标准化疗联合尼洛替尼获得显著的无疾病进展生存时间。通过分析认为表皮生长因子受体抑制剂有效地控制胆道肿瘤进展,有望成为靶向治疗的新方向。

Molecular targeted therapy has become a new hot spot with the in -depth basic research on advanced biliary tract cancer （ABTC）.Phase ⅡandⅢtrials of the molecular targeted therapies for ABTC are summarized to provide new insights into clinical practice. Phase II trials have shown that vascular endothelial growth factor receptor inhibitor and mitogen-activated protein kinase inhibitor do not exhibit good anti-tumor activity,but epidermal growth factor receptor （EGFR）inhibitor has proven to be safe and effective in the treatment of ABTC.The only multicenter,open-label,randomized,controlled phase Ⅲ trial has shown that nilotinib combined with gemcitabine and oxaliplatin,as the first-line chemotherapy for ABTC,cannot significantly increase the overall survival in patients.Subgroup analysis has shown that standard chemotherapy combined with nilotinib can significantly increase the progression-free survival in patients.These results indicate that EGFR inhibitor is effective to control the progression of ABTC,suggesting that EGFR might be a novel therapeutic target.