Research advances in molecular targeted therapy for advanced biliary tract cancer
-
摘要: 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。Abstract: Molecular targeted therapy has become a new hot spot with the in- depth basic research on advanced biliary tract cancer (ABTC) . Phase Ⅱ and Ⅲ trials 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.
-
[1] SIEGEL R, NAISHADHAM D, JEMAL A.Cancer statistics, 2012[J].CA Cancer J Clin, 2012, 62 (1) :10-29. [2]KHAN SA, DAVIDSON BR, GOLDIN RD, et al.Guidelines for the diagnosis and treatment of cholangiocarcinoma:an update[J].Gut, 2012, 61 (12) :1657-1669. [3]BRIDGEWATER J, GALLE PR, KHAN SA, et al.Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma[J].J Hepatol, 2014, 60 (6) :1268-1289. [4] VALLE J, WASAN H, PALMER DH, et al.Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J].New Engl J Med, 2010, 362 (14) :1273-1281. [5]ZHU AX, HEZEL AF.Development of molecularly targeted therapies in biliary tract cancers:reassessing the challenges and opportunities[J].Hepatology, 2011, 53 (2) :695-704. [6]FRATTO ME, SANTINI D, VINCENZI B, et al.Targeting EGFR in bilio-pancreatic and liver carcinoma[J].Front Biosci (Schol Ed) , 2011, 3:16-22. [7]XU L, HAUSMANN M, DIETMAIER W, et al.Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines[J].BMC Cancer, 2010, 10:302. [8]CHEN Y, JIANG L, SHE F, et al.Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism[J].Mol Cell Biochem, 2010, 345 (1-2) :77-89. [9]RIZVI S, GORES GJ.Pathogenesis, diagnosis, and management of cholangiocarcinoma[J].Gastroenterology, 2013, 145 (6) :1215-1229. [10] PHILIP PA, MAHONEY MR, ALLMER C, et al.Phase II study of erlotinib in patients with advanced biliary cancer[J].J Clin Oncol, 2006, 24 (19) :3069-3074. [11]EL-KHOUEIRY AB, RANKIN C, SIEGEL AB, et al.S0941:a phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma[J].Br J Cancer, 2014, 110 (4) :882-887. [12]LUBNER SJ, MAHONEY MR, KOLESAR JL, et al.Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer:a phase II Consortium study[J].J Clin Oncol, 2010, 28 (21) :3491-3497. [13]LEE J, PARK SH, CHANG HM, et al.Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer:a multicentre, open-label, randomised, phase 3 study[J].Lancet Oncol, 2012, 13 (2) :181-188. [14]PECK J, WEI L, ZALUPSKI M, et al.HER2/neu may not be an interesting target in biliary cancers:results of an early phase II study with lapatinib[J].Oncology, 2012, 82 (3) :175-179. [15]PIGNOCHINO Y, SAROTTO I, PERALDO-NEIA C, et al.Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas[J].BMC Cancer, 2010, 10:631. [16]YOSHIKAWA D, OJIMA H, IWASAKI M, et al.Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma[J].Br J Cancer, 2008, 98 (2) :418-425. [17]GRUENBERGER B, SCHUELLER J, HEUBRANDTNER U, et al.Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer:a phase 2 study[J].Lancet Oncol, 2010, 11 (12) :1142-1148. [18]RUBOVSZKY G, LANG I, GANOFSZKY E, et al.Cetuximab, gemcitabine and capecitabine in patients with inoperable biliary tract cancer:a phase 2 study[J].Eur J Cancer, 2013, 49 (18) :3806-3812. [19]MALKA D, CERVERA P, FOULON S, et al.Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO) :a randomised, open-label, non-comparative phase 2trial[J].Lancet Oncol, 2014, 15 (8) :819-828. [20]JENSEN LH, LINDEBJERG J, PLOEN J, et al.PhaseⅡmarker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer[J].Ann Oncol, 2012, 23 (9) :2341-2346. [21]SOHAL DP, MYKULOWYCZ K, UEHARA T, et al.A phaseⅡtrial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma[J].Ann Oncol, 2013, 24 (12) :3061-3065. [22]ZHU AX, MEYERHARDT JA, BLASZKOWSKY LS, et al.Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome:a phase 2 study[J].Lancet Oncol, 2010, 11 (1) :48-54. [23]EL-KHOUEIRY AB, RANKIN CJ, BEN-JOSEF E, et al.SWOG0514:a phaseⅡstudy of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma[J].Invest New Drugs, 2012, 30 (4) :1646-1651. [24] BENGALA C, BERTOLINI F, MALAVASI N, et al.Sorafenib in patients with advanced biliary tract carcinoma:a phase II trial[J].Br J Cancer, 2010, 102 (1) :68-72. [25]LEE JK, CAPANU M, O'REILLY EM, et al.A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas[J].Br J Cancer, 2013, 109 (4) :915-919. [26]YI JH, THONGPRASERT S, LEE J, et al.A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma:a multicentre, multinational study[J].Eur J Cancer, 2012, 48 (2) :196-201. [27]BEKAII-SAAB T, PHELPS MA, LI X, et al.Multi-institutional phaseⅡstudy of selumetinib in patients with metastatic biliary cancers[J].J Clin Oncol, 2011, 29 (17) :2357-2363.
本文二维码
计量
- 文章访问数: 2491
- HTML全文浏览量: 18
- PDF下载量: 574
- 被引次数: 0