老年晚期胃癌的靶向治疗新进展
摘要
<正>胃癌是全世界第五大常见的恶性肿瘤,尤其是在亚洲发病率更高,据报道,死于胃癌的患者居2012年癌致死亡原因的第3位~([1])。虽然当前胃癌的治疗方法很多,但是由于胃癌发现较晚,错过了最佳的手术时间,且诸多患者对放化疗极易产生耐药性。因此靶向治疗成为临床治疗胃癌尤其是晚期胃癌的最主要二线药物~([2])。研究表明,血管内皮生长因子(VEGF)和VEGF受体(VEGFR)-2介导的血管生成信号传导通路有助于胃癌的发生发展~([3])。目前,靶向药物主要针对抑
引文
1 Ferlay J,Soerjomataram I,Dikshit R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].Int J Cancer,2015;136:e359-86.
2 Li K,Li J.Current molecular targeted therapy in advanced gastric cancer:a comprehensive review of therapeutic mechanism,clinical trials,and practical application[J].Gastroenterol Res Pract,2016;2016:4105615.
3 Chen LT,Oh DY,Ryu MH,et al.Anti-angiogenic therapy in patients with advanced gastric and gastroesophageal junction cancer:a systematic review[J].Cancer Res Treat,2017;49(4):851-68.
4 冯睿,张小田,杨升.胃癌靶向治疗的研究现状与进展[J].中华胃肠外科杂质,2016;19(10):1191-6.
5 Wang H,Li B,Liu Z,et al.HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer[J].Eur J Cancer,2018;88:92-100.
6 Li Q,Li H,Jiang H,et al.Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer:a single-center prospective observational study[J].Clin Transla Oncol,2017;(1):1-8.
7 Kimura Y,Fujii M,Masuishi T,et al.Multicenter phase Ⅱ study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer(JACCRO GC-06)[J].Gastric Cancer,2018;21(3):421-7.
8 Kagawa S,Muraoka A,Kambara T,et al.A multi-institution phase Ⅱ study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer(DASH study)[J].Cancer Chemother Pharmacol,2018;81(2):387-92.
9 Xu C,Liu Y,Jiang D,et al.Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type[J].Oncotarget,2017;8(20):33185-96.
10 Huang L,Wei Y,Shen S,et al.Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients[J].Oncotarget,2017;8(17):29346-54.
11 Chen HD,Zhou J,Wen F,et al.Cost-effectiveness analysis of apatinib treatment for chemotherapy-refractory advanced gastric cancer[J].J Cancer Res Clin Oncol,2017;143(2):361-8.
12 Zhang Y,Han C,Li J,et al.Efficacy and safety for Apatinib treatment in advanced gastric cancer:a real world study[J].Sci Rep,2017;7(1):13208.
13 Zhang M,Deng W,Cao X,et al.Concurrent apatinib and local radiation therapy for advanced gastric cancer:a case report and review of the literature[J].Medicine,2017;96(9):e6241.
14 Cheng R,Yong H,Xia Y,et al.Chemotherapy regimen based on sorafenib combined with 5-FU on HIF-1alpha and VEGF expression and survival in advanced gastric cancer patients[J].Oncol Lett,2017;13(4):2703-7.
15 Chi Y,Yang J,Yang S,et al.Phase Ⅰ dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer[J].Chin J Cancer Res,2015;27(3):239-46.
16 Moehler M,Gepfner-Tuma I,Maderer A,et al.Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus:a randomized,placebo-controlled phase Ⅱ AIO trial with serum biomarker program[J].Bmc Cancer,2016;16(1):699.
17 王清华,叶木林,刘倩,等.依维莫司和舒尼替尼联用提高抗胃癌活性的机制[J].中国老年学杂志,2017;37(12):2897-9.
18 Pavlakis N,Sjoquist KM,Martin AJ,et al.Regorafenib for the treatment of advanced gastric cancer(INTEGRATE):a multinational placebo-controlled phase Ⅱ trial[J].J Clin Oncol,2016;34(23):2728-35.
19 Mawalla B,Yuan X,Luo X,et al.Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer:a systematic review of phase Ⅱ and Ⅲ clinical trials[J].BMC Res Notes,2018;11(1):21.
20 Kim JH,Park SR,Ryu MH,et al.Phase Ⅱ study of induction chemotherapy with docetaxel,capecitabine,and cisplatin plus bevacizumab for initially unresectable gastric cancer with invasion of adjacent organs or paraaortic lymph node metastasis[J].Cancer Res Treat,2018;50(2):518-29.
21 Woll E,Thaler J,Keil F,et al.Oxaliplatin/Irinotecan/Bevacizumab Followed by Docetaxel/Bevacizumab in inoperable locally advanced or metastatic gastric cancer patients-AGMT_GASTRIC-3[J].Anticancer Res,2017;37(10):5553-8.
22 Hacker UT,Escalona-Espinosa L,Consalvo N,et al.Evaluation of Angiopoietin-2 as a biomarker in gastric cancer:results from the randomised phase Ⅲ AVAGAST trial[J].Br J Cancer,2016;114(8):855-62.
23 Cunningham D,Stenning SP,Smyth EC,et al.Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma(UK Medical Research Council ST03):primary analysis results of a multicentre,open-label,randomised phase 2-3 trial[J].Lancet Oncol,2017;18(3):357-70.
24 Buyukkaramikli NC,Blommestein HM,Riemsma R,et al.Ramucirumab for treating advanced gastric cancer or gastro-oesophageal junction adenocarcinoma previously treated with chemotherapy:an evidence review group perspective of a NICE single technology appraisal[J].Pharmacoeconomics,2017;35(12):1211-21.
25 Saito S,Muneoka Y,Ishikawa T,et al.Cost-effectiveness of Paclitaxel+ Ramucirumab combination therapy for advanced gastric cancer progressing after first-line chemotherapy in Japan[J].Clin Ther,2017;39(12):2380-8.
26 Muro K,Oh SC,Shimada Y,et al.Subgroup analysis of east Asians in RAINBOW:a phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer[J].J Gastroenterol Hepatol,2016;31(3):581-9.
27 Muro K,Cho JY,Bodoky G,et al.Age does not influence efficacy of ramucirumab in advanced gastric cancer:subgroup analyses of REGARD and RAINBOW[J].J Gastroenterol Hepatol,2018;33(4):814-24.
2 Li K,Li J.Current molecular targeted therapy in advanced gastric cancer:a comprehensive review of therapeutic mechanism,clinical trials,and practical application[J].Gastroenterol Res Pract,2016;2016:4105615.
3 Chen LT,Oh DY,Ryu MH,et al.Anti-angiogenic therapy in patients with advanced gastric and gastroesophageal junction cancer:a systematic review[J].Cancer Res Treat,2017;49(4):851-68.
4 冯睿,张小田,杨升.胃癌靶向治疗的研究现状与进展[J].中华胃肠外科杂质,2016;19(10):1191-6.
5 Wang H,Li B,Liu Z,et al.HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer[J].Eur J Cancer,2018;88:92-100.
6 Li Q,Li H,Jiang H,et al.Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer:a single-center prospective observational study[J].Clin Transla Oncol,2017;(1):1-8.
7 Kimura Y,Fujii M,Masuishi T,et al.Multicenter phase Ⅱ study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer(JACCRO GC-06)[J].Gastric Cancer,2018;21(3):421-7.
8 Kagawa S,Muraoka A,Kambara T,et al.A multi-institution phase Ⅱ study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer(DASH study)[J].Cancer Chemother Pharmacol,2018;81(2):387-92.
9 Xu C,Liu Y,Jiang D,et al.Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type[J].Oncotarget,2017;8(20):33185-96.
10 Huang L,Wei Y,Shen S,et al.Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients[J].Oncotarget,2017;8(17):29346-54.
11 Chen HD,Zhou J,Wen F,et al.Cost-effectiveness analysis of apatinib treatment for chemotherapy-refractory advanced gastric cancer[J].J Cancer Res Clin Oncol,2017;143(2):361-8.
12 Zhang Y,Han C,Li J,et al.Efficacy and safety for Apatinib treatment in advanced gastric cancer:a real world study[J].Sci Rep,2017;7(1):13208.
13 Zhang M,Deng W,Cao X,et al.Concurrent apatinib and local radiation therapy for advanced gastric cancer:a case report and review of the literature[J].Medicine,2017;96(9):e6241.
14 Cheng R,Yong H,Xia Y,et al.Chemotherapy regimen based on sorafenib combined with 5-FU on HIF-1alpha and VEGF expression and survival in advanced gastric cancer patients[J].Oncol Lett,2017;13(4):2703-7.
15 Chi Y,Yang J,Yang S,et al.Phase Ⅰ dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer[J].Chin J Cancer Res,2015;27(3):239-46.
16 Moehler M,Gepfner-Tuma I,Maderer A,et al.Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus:a randomized,placebo-controlled phase Ⅱ AIO trial with serum biomarker program[J].Bmc Cancer,2016;16(1):699.
17 王清华,叶木林,刘倩,等.依维莫司和舒尼替尼联用提高抗胃癌活性的机制[J].中国老年学杂志,2017;37(12):2897-9.
18 Pavlakis N,Sjoquist KM,Martin AJ,et al.Regorafenib for the treatment of advanced gastric cancer(INTEGRATE):a multinational placebo-controlled phase Ⅱ trial[J].J Clin Oncol,2016;34(23):2728-35.
19 Mawalla B,Yuan X,Luo X,et al.Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer:a systematic review of phase Ⅱ and Ⅲ clinical trials[J].BMC Res Notes,2018;11(1):21.
20 Kim JH,Park SR,Ryu MH,et al.Phase Ⅱ study of induction chemotherapy with docetaxel,capecitabine,and cisplatin plus bevacizumab for initially unresectable gastric cancer with invasion of adjacent organs or paraaortic lymph node metastasis[J].Cancer Res Treat,2018;50(2):518-29.
21 Woll E,Thaler J,Keil F,et al.Oxaliplatin/Irinotecan/Bevacizumab Followed by Docetaxel/Bevacizumab in inoperable locally advanced or metastatic gastric cancer patients-AGMT_GASTRIC-3[J].Anticancer Res,2017;37(10):5553-8.
22 Hacker UT,Escalona-Espinosa L,Consalvo N,et al.Evaluation of Angiopoietin-2 as a biomarker in gastric cancer:results from the randomised phase Ⅲ AVAGAST trial[J].Br J Cancer,2016;114(8):855-62.
23 Cunningham D,Stenning SP,Smyth EC,et al.Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma(UK Medical Research Council ST03):primary analysis results of a multicentre,open-label,randomised phase 2-3 trial[J].Lancet Oncol,2017;18(3):357-70.
24 Buyukkaramikli NC,Blommestein HM,Riemsma R,et al.Ramucirumab for treating advanced gastric cancer or gastro-oesophageal junction adenocarcinoma previously treated with chemotherapy:an evidence review group perspective of a NICE single technology appraisal[J].Pharmacoeconomics,2017;35(12):1211-21.
25 Saito S,Muneoka Y,Ishikawa T,et al.Cost-effectiveness of Paclitaxel+ Ramucirumab combination therapy for advanced gastric cancer progressing after first-line chemotherapy in Japan[J].Clin Ther,2017;39(12):2380-8.
26 Muro K,Oh SC,Shimada Y,et al.Subgroup analysis of east Asians in RAINBOW:a phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer[J].J Gastroenterol Hepatol,2016;31(3):581-9.
27 Muro K,Cho JY,Bodoky G,et al.Age does not influence efficacy of ramucirumab in advanced gastric cancer:subgroup analyses of REGARD and RAINBOW[J].J Gastroenterol Hepatol,2018;33(4):814-24.