胃癌化疗的现状与研究进展
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摘要
胃癌是全球范围内最常见的恶性肿瘤之一,发病率及死亡均居高不下,目前,无论早期胃癌的术后辅助治疗,还是晚期胃癌的维持治疗,均以化疗为主。近年来,靶向治疗及免疫治疗等多种新型治疗手段的发展,也为胃癌的药物治疗提供了更多的选择。本文对胃癌的药物治疗进展进行综述。
Gastric cancer is one of the most common malignant tumors in the world,with high morbidity and mortality.Currently,chemotherapy is the main treatment for both postoperative adjuvant therapy for early gastric cancer and maintenance therapy for advanced gastric cancer.In recent years,the development of new therapeutic methods such as targeted therapy and immunotherapy also provides more options for the drug treatment of gastric cancer.This article reviews the progress of drug treatment for gastric cancer.
Gastric cancer is one of the most common malignant tumors in the world,with high morbidity and mortality.Currently,chemotherapy is the main treatment for both postoperative adjuvant therapy for early gastric cancer and maintenance therapy for advanced gastric cancer.In recent years,the development of new therapeutic methods such as targeted therapy and immunotherapy also provides more options for the drug treatment of gastric cancer.This article reviews the progress of drug treatment for gastric cancer.
引文
[1] Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[2] Webb A,Cunningham D,Scarffe JH,et al.Randomized trial comparing epirubicin,cisplatin,and fluorouracil versus fluorouracil,doxorubicin,and methotrexate in advanced esophagogastric cancer[J].J Clin Oncol,1997,15(1):261-267.
[3] Ross P,Nicolson M,Cunningham D,et al.Prospective randomized trial comparing mitomycin,cisplatin,and protracted venous-infusion fluorouracil(PVI 5-FU)with epirubicin,cisplatin,and PVI 5-FU in advanced esophagogastric cancer[J].J Clin Oncol,2002,20(8):1996-2004.
[4] Waters JS,Norman A,Cunningham D,et al.Long-term survival after epirubicin,cisplatin and fluorouracil for gastric cancer:results of a randomized trial[J].Br J Cancer,1999,80(1-2):269-272.
[5] Cunningham D,Allum WH,Stenning SP,et al.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer[J].N Engl J Med,2006,355(1):11-20.
[6] Ychou M,Boige V,Pignon JP,et al.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma:an FNCLCC and FFCD multicenter phase III trial[J].J Clin Oncol,2011,29(13):1715-1721.
[7] Schuhmacher C,Gretschel S,Lordick F,et al.Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia:European Organisation for Research and Treatment of Cancer randomized trial 40954[J].J Clin Oncol,2010,28(35):5210-5218.
[8] Noh SH,Park SR,Yang HK,et al.Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy(CLASSIC):5-year follow-up of an open-label,randomised phase 3 trial[J].Lancet Oncol,2014,15(12):1389-1396.
[9] Sasako M,Sakuramoto S,Katai H,et al.Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer[J].J Clin Oncol,2011,29(33):4387-4393.
[10] Tsuburaya A,Yoshida K,Kobayashi M,et al.Sequential paclitaxel followed by tegafur and uracil(UFT)or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer(SAMIT):a phase 3 factorial randomised controlled trial[J].Lancet Oncol,2014,15(8):886-893.
[11] Lee J,Lim DH,Kim S,et al.Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection:the ARTIST trial[J].J Clin Oncol,2012,30(3):268-273.
[12] Wagner AD,Unverzagt S,Grothe W,et al.Chemotherapy for advanced gastric cancer[J].Cochrane Database Syst Rev,2010,(3):CD004064.
[13] Preusser P,Wilke H,Achterrath W,et al.Phase II study of carboplatin in untreated inoperable advanced stomach cancer[J].Eur J Cancer,1990,26(10):1108-1109.
[14] Al-Batran SE,Hartmann JT,Probst S,et al.Phase III trial in metastatic gastro-esophageal adenocarcinoma with fluorouracil,leucovorin plus either oxaliplatin or cisplatin:a study of the Arbeitsgemeinschaft Internistische Onkologie[J].J Clin Oncol,2008,26(9):1435-1442.
[15] Guimbaud R,Louvet C,Ries P,et al.Prospective,randomized,multicenter,phase III study of fluorouracil,leucovorin,and irinotecan versus epirubicin,cisplatin,and capecitabine in advanced gastric adenocarcinoma:a French intergroup(Fédération Francophone de Cancérologie Digestive,Fédération Nationale des Centres de Lutte Contre le Cancer,and Groupe Coopérateur Multidisciplinaire en Oncologie)study[J].J Clin Oncol,2014,32(31):3520-3526.
[16] Cunningham D,Starling N,Rao S,et al.Capecitabine and oxaliplatin for advanced esophagogastric cancer[J].N Engl J Med,2008,358(1):36-46.
[17] Kang YK,Kang WK,Shin DB,et al.Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer:a randomised phase III noninferiority trial[J].Ann Oncol,2009,20(4):666-673.
[18] Wagner AD,Grothe W,Haerting J,et al.Chemotherapy in advanced gastric cancer:a systematic review and meta-analysis based on aggregate data[J].J Clin Oncol,2006,24(18):2903-2909.
[19] Van Cutsem E,Moiseyenko VM,Tjulandin S,et al.Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer:a report of the V325 Study Group[J].J Clin Oncol,2006,24(31):4991-4997.
[20] He MM,Wu WJ,Wang F,et al.S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for advanced gastric carcinoma:a meta-analysis[J].PLoS One,2013,8(12):e82798.
[21] Ajani JA,Moiseyenko VM,Tjulandin S,et al.Quality of life with docetaxel plus cisplatin and fluorouracil compared with cisplatin and fluorouracil from a phase III trial for advanced gastric or gastroesophageal adenocarcinoma:the V-325 Study Group[J].J Clin Oncol,2007,25(22):3210-3216.
[22] Lorenzen S,Hentrich M,Haberl C,et al.Split-dose docetaxel,cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction:results of a phase II trial[J].Ann Oncol,2007,18(10):1673-1679.
[23] Shah MA,Janjigian YY,Stoller R,et al.Randomized multicenter phase II study of modified docetaxel,cisplatin,and fluorouracil(DCF)versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma:a study of the US gastric cancer consortium[J].J Clin Oncol,2015,33(33):3874-3879.
[24] Tebbutt NC,Cummins MM,Sourjina T,et al.Randomised,non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer:the AGITG ATTAX trial[J].Br J Cancer,2010,102(3):475-481.
[25] Al-Batran SE,Hartmann JT,Hofheinz R,et al.Biweekly fluorouracil,leucovorin,oxaliplatin,and docetaxel(FLOT)for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction:a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie[J].Ann Oncol,2008,19(11):1882-1887.
[26] Van Cutsem E,Boni C,Tabernero J,et al.Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer:a randomized phase II study[J].Ann Oncol,2015,26(1):149-156.
[27] Bang YJ,Van Cutsem E,Feyereislova A,et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):a phase 3,open-label,randomised controlled trial[J].Lancet,2010,376(9742):687-697.
[28] Ryu MH,Yoo C,Kim JG,et al.Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer[J].Eur J Cancer,2015,51(4):482-488.
[29] Soularue é,Cohen R,Tournigand C,et al.Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients:a retrospective study[J].Bull Cancer,2015,102(4):324-331.
[30] Gong J,Liu T,Fan Q,et al.Optimal regimen of trastuzumab in combination with oxaliplatin/capecitabine in first-line treatment of HER2-positive advanced gastric cancer(CGOG1001):a multicenter,phase II trial[J].BMC Cancer,2016,16:68.
[31] Hecht JR,Bang YJ,Qin SK,et al.Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric,esophageal,or gastroesophageal adenocarcinoma:TRIO-013/LOGiC-a randomized phase III Trial[J].J Clin Oncol,2016,34(5):443-451.
[32] Satoh T,Xu RH,Chung HC,et al.Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations:TyTAN--a randomized,phase III study[J].J Clin Oncol,2014,32(19):2039-2049.
[33] Thallinger CM,Raderer M,Hejna M.Esophageal cancer:a critical evaluation of systemic second-line therapy[J].J Clin Oncol,2011,29(35):4709-4714.
[34] Thuss-Patience PC,Kretzschmar A,Bichev D,et al.Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie(AIO)[J].Eur J Cancer,2011,47(15):2306-2314.
[35] Kang JH,Lee SI,Lim DH,et al.Salvage chemotherapy for pretreated gastric cancer:a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone[J].J Clin Oncol,2012,30(13):1513-1518.
[36] Ford HE,Marshall A,Bridgewater JA,et al.Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma(COUGAR-02):an open-label,phase 3 randomised controlled trial[J].Lancet Oncol,2014,15(1):78-86.
[37] Hironaka S,Ueda S,Yasui H,et al.Randomized,open-label,phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum:WJOG 4007 trial[J].J Clin Oncol,2013,31(35):4438-4444.
[38] Jayson GC,Kerbel R,Ellis LM,et al.Antiangiogenic therapy in oncology:current status and future directions[J].Lancet,2016,388(10043):518-529.
[39] Fuchs CS,Tomasek J,Yong CJ,et al.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD):an international,randomised,multicentre,placebo-controlled,phase 3 trial[J].Lancet,2014,383(9911):31-39.
[40] Wilke H,Muro K,Van Cutsem E,et al.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(RAINBOW):a double-blind,randomised phase 3 trial[J].Lancet Oncol,2014,15(11):1224-1235.
[41] Al-Batran SE,Van Cutsem E,Oh SC,et al.Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plusvpaclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma[J].Ann Oncol,2016,27(4):673-679.
[42] Lorenzen S,Riera KJ,Haag GM,et al.Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer:a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie[J].Eur J Cancer,2015,51(5):569-576.
[43] Kang YK,Shah MA,Ohtsu A,et al.A randomized,open-label,multicenter,adaptive phase 2/3 study of trastuzumab emtansine(T-DM1)versus a taxane(TAX)inpatients(pts)with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma(LA/MGC/GEJC)[J].J Clin Oncol,2016,34(supple 4).
[2] Webb A,Cunningham D,Scarffe JH,et al.Randomized trial comparing epirubicin,cisplatin,and fluorouracil versus fluorouracil,doxorubicin,and methotrexate in advanced esophagogastric cancer[J].J Clin Oncol,1997,15(1):261-267.
[3] Ross P,Nicolson M,Cunningham D,et al.Prospective randomized trial comparing mitomycin,cisplatin,and protracted venous-infusion fluorouracil(PVI 5-FU)with epirubicin,cisplatin,and PVI 5-FU in advanced esophagogastric cancer[J].J Clin Oncol,2002,20(8):1996-2004.
[4] Waters JS,Norman A,Cunningham D,et al.Long-term survival after epirubicin,cisplatin and fluorouracil for gastric cancer:results of a randomized trial[J].Br J Cancer,1999,80(1-2):269-272.
[5] Cunningham D,Allum WH,Stenning SP,et al.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer[J].N Engl J Med,2006,355(1):11-20.
[6] Ychou M,Boige V,Pignon JP,et al.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma:an FNCLCC and FFCD multicenter phase III trial[J].J Clin Oncol,2011,29(13):1715-1721.
[7] Schuhmacher C,Gretschel S,Lordick F,et al.Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia:European Organisation for Research and Treatment of Cancer randomized trial 40954[J].J Clin Oncol,2010,28(35):5210-5218.
[8] Noh SH,Park SR,Yang HK,et al.Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy(CLASSIC):5-year follow-up of an open-label,randomised phase 3 trial[J].Lancet Oncol,2014,15(12):1389-1396.
[9] Sasako M,Sakuramoto S,Katai H,et al.Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer[J].J Clin Oncol,2011,29(33):4387-4393.
[10] Tsuburaya A,Yoshida K,Kobayashi M,et al.Sequential paclitaxel followed by tegafur and uracil(UFT)or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer(SAMIT):a phase 3 factorial randomised controlled trial[J].Lancet Oncol,2014,15(8):886-893.
[11] Lee J,Lim DH,Kim S,et al.Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection:the ARTIST trial[J].J Clin Oncol,2012,30(3):268-273.
[12] Wagner AD,Unverzagt S,Grothe W,et al.Chemotherapy for advanced gastric cancer[J].Cochrane Database Syst Rev,2010,(3):CD004064.
[13] Preusser P,Wilke H,Achterrath W,et al.Phase II study of carboplatin in untreated inoperable advanced stomach cancer[J].Eur J Cancer,1990,26(10):1108-1109.
[14] Al-Batran SE,Hartmann JT,Probst S,et al.Phase III trial in metastatic gastro-esophageal adenocarcinoma with fluorouracil,leucovorin plus either oxaliplatin or cisplatin:a study of the Arbeitsgemeinschaft Internistische Onkologie[J].J Clin Oncol,2008,26(9):1435-1442.
[15] Guimbaud R,Louvet C,Ries P,et al.Prospective,randomized,multicenter,phase III study of fluorouracil,leucovorin,and irinotecan versus epirubicin,cisplatin,and capecitabine in advanced gastric adenocarcinoma:a French intergroup(Fédération Francophone de Cancérologie Digestive,Fédération Nationale des Centres de Lutte Contre le Cancer,and Groupe Coopérateur Multidisciplinaire en Oncologie)study[J].J Clin Oncol,2014,32(31):3520-3526.
[16] Cunningham D,Starling N,Rao S,et al.Capecitabine and oxaliplatin for advanced esophagogastric cancer[J].N Engl J Med,2008,358(1):36-46.
[17] Kang YK,Kang WK,Shin DB,et al.Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer:a randomised phase III noninferiority trial[J].Ann Oncol,2009,20(4):666-673.
[18] Wagner AD,Grothe W,Haerting J,et al.Chemotherapy in advanced gastric cancer:a systematic review and meta-analysis based on aggregate data[J].J Clin Oncol,2006,24(18):2903-2909.
[19] Van Cutsem E,Moiseyenko VM,Tjulandin S,et al.Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer:a report of the V325 Study Group[J].J Clin Oncol,2006,24(31):4991-4997.
[20] He MM,Wu WJ,Wang F,et al.S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for advanced gastric carcinoma:a meta-analysis[J].PLoS One,2013,8(12):e82798.
[21] Ajani JA,Moiseyenko VM,Tjulandin S,et al.Quality of life with docetaxel plus cisplatin and fluorouracil compared with cisplatin and fluorouracil from a phase III trial for advanced gastric or gastroesophageal adenocarcinoma:the V-325 Study Group[J].J Clin Oncol,2007,25(22):3210-3216.
[22] Lorenzen S,Hentrich M,Haberl C,et al.Split-dose docetaxel,cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction:results of a phase II trial[J].Ann Oncol,2007,18(10):1673-1679.
[23] Shah MA,Janjigian YY,Stoller R,et al.Randomized multicenter phase II study of modified docetaxel,cisplatin,and fluorouracil(DCF)versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma:a study of the US gastric cancer consortium[J].J Clin Oncol,2015,33(33):3874-3879.
[24] Tebbutt NC,Cummins MM,Sourjina T,et al.Randomised,non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer:the AGITG ATTAX trial[J].Br J Cancer,2010,102(3):475-481.
[25] Al-Batran SE,Hartmann JT,Hofheinz R,et al.Biweekly fluorouracil,leucovorin,oxaliplatin,and docetaxel(FLOT)for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction:a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie[J].Ann Oncol,2008,19(11):1882-1887.
[26] Van Cutsem E,Boni C,Tabernero J,et al.Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer:a randomized phase II study[J].Ann Oncol,2015,26(1):149-156.
[27] Bang YJ,Van Cutsem E,Feyereislova A,et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):a phase 3,open-label,randomised controlled trial[J].Lancet,2010,376(9742):687-697.
[28] Ryu MH,Yoo C,Kim JG,et al.Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer[J].Eur J Cancer,2015,51(4):482-488.
[29] Soularue é,Cohen R,Tournigand C,et al.Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients:a retrospective study[J].Bull Cancer,2015,102(4):324-331.
[30] Gong J,Liu T,Fan Q,et al.Optimal regimen of trastuzumab in combination with oxaliplatin/capecitabine in first-line treatment of HER2-positive advanced gastric cancer(CGOG1001):a multicenter,phase II trial[J].BMC Cancer,2016,16:68.
[31] Hecht JR,Bang YJ,Qin SK,et al.Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric,esophageal,or gastroesophageal adenocarcinoma:TRIO-013/LOGiC-a randomized phase III Trial[J].J Clin Oncol,2016,34(5):443-451.
[32] Satoh T,Xu RH,Chung HC,et al.Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations:TyTAN--a randomized,phase III study[J].J Clin Oncol,2014,32(19):2039-2049.
[33] Thallinger CM,Raderer M,Hejna M.Esophageal cancer:a critical evaluation of systemic second-line therapy[J].J Clin Oncol,2011,29(35):4709-4714.
[34] Thuss-Patience PC,Kretzschmar A,Bichev D,et al.Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie(AIO)[J].Eur J Cancer,2011,47(15):2306-2314.
[35] Kang JH,Lee SI,Lim DH,et al.Salvage chemotherapy for pretreated gastric cancer:a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone[J].J Clin Oncol,2012,30(13):1513-1518.
[36] Ford HE,Marshall A,Bridgewater JA,et al.Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma(COUGAR-02):an open-label,phase 3 randomised controlled trial[J].Lancet Oncol,2014,15(1):78-86.
[37] Hironaka S,Ueda S,Yasui H,et al.Randomized,open-label,phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum:WJOG 4007 trial[J].J Clin Oncol,2013,31(35):4438-4444.
[38] Jayson GC,Kerbel R,Ellis LM,et al.Antiangiogenic therapy in oncology:current status and future directions[J].Lancet,2016,388(10043):518-529.
[39] Fuchs CS,Tomasek J,Yong CJ,et al.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(REGARD):an international,randomised,multicentre,placebo-controlled,phase 3 trial[J].Lancet,2014,383(9911):31-39.
[40] Wilke H,Muro K,Van Cutsem E,et al.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma(RAINBOW):a double-blind,randomised phase 3 trial[J].Lancet Oncol,2014,15(11):1224-1235.
[41] Al-Batran SE,Van Cutsem E,Oh SC,et al.Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plusvpaclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma[J].Ann Oncol,2016,27(4):673-679.
[42] Lorenzen S,Riera KJ,Haag GM,et al.Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer:a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie[J].Eur J Cancer,2015,51(5):569-576.
[43] Kang YK,Shah MA,Ohtsu A,et al.A randomized,open-label,multicenter,adaptive phase 2/3 study of trastuzumab emtansine(T-DM1)versus a taxane(TAX)inpatients(pts)with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma(LA/MGC/GEJC)[J].J Clin Oncol,2016,34(supple 4).