胃癌的分子靶向治疗
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摘要
胃癌的死亡率在全球癌症死亡率中居第二位,我国胃癌的年死亡率在各种恶性肿瘤中占首位。随着外科手术技术的提高、传统放化疗技术的进步以及新辅助疗法的实施,早期胃癌的5年生存率可达95%以上。然而,大多数胃癌患者确诊时疾病已进入晚期,此时传统的治疗手段都不能有效降低患者的死亡率,应采用包括手术、化疗、放疗及免疫治疗等在内的综合治疗措施。近年来一种新的治疗模式——肿瘤分子靶向治疗在抗肿瘤治疗中发挥着日益重要的作用,并显示出良好的应用前景。这些策略主要包括表皮生长因子受体抑制剂、Her-2受体抑制剂、抗血管生成因子、细胞周期抑制剂、细胞凋亡促进剂等。本文就胃癌的分子靶向治疗进行综述,用于指导进展期胃癌,尤其是不能切除或姑息性切除胃癌患者的治疗,以延长患者的生存期,提高患者的生活质量。
Gastric cancer is the second leading cause of cancer mortality worldwide and is a major cause of cancer death in China.Recent improvements in both surgical techniques and adjuvant/neoadjuvant chemotherapy,radiotherapy or both have increased the survival rate of patients with early-stage disease.As most cases of gastric cancer are in the advanced stage of the disease when they are first diagnosed,patients receiving conventional therapies have poor prognosis.An emerging modality called tumor molecular targeted therapy provides promise and insight to combat this malignancy.These therapeutic strategies include epidermal growth factor receptor inhibitors,Her-2 receptor inhibitors,angiogenesis inhibitors,cell cycle inhibitors and apoptosis promoters.This review that presents a brief introduction to molecular targeted therapy of gastric cancer was intended to play a guidance in the therapy of advanced gastric cancer.Its significance is to prolong survival time and improve life quality of patients.
Gastric cancer is the second leading cause of cancer mortality worldwide and is a major cause of cancer death in China.Recent improvements in both surgical techniques and adjuvant/neoadjuvant chemotherapy,radiotherapy or both have increased the survival rate of patients with early-stage disease.As most cases of gastric cancer are in the advanced stage of the disease when they are first diagnosed,patients receiving conventional therapies have poor prognosis.An emerging modality called tumor molecular targeted therapy provides promise and insight to combat this malignancy.These therapeutic strategies include epidermal growth factor receptor inhibitors,Her-2 receptor inhibitors,angiogenesis inhibitors,cell cycle inhibitors and apoptosis promoters.This review that presents a brief introduction to molecular targeted therapy of gastric cancer was intended to play a guidance in the therapy of advanced gastric cancer.Its significance is to prolong survival time and improve life quality of patients.
引文
1 Parkin DM,Pisani P,Ferlay J,Estimates of the worldwide incidence of eighteen major cancers in 1985.Int J Cancer,1993,54(4):594-606
2 Parkin DM,Bray FI,Devesa SS.Cancer burden in the year 2000.The global picture.Eur J Cancer,2001,37(Suppl 8):S4-S66
3詹友庆,李威,孙晓卫,等胃癌外科治疗的远期疗效研究.中华外科杂志, 2005,43(17):1109
4 MU FSON RA.Tumor antigen targets and tumor immunotherapy.Front Biosci,2006,11:337-343
5 Sako Y,Minoghchi S,Yanagida T.Single-molecule imaging of EGFR signaling on the surface of living cells.Nat Cell Biol,2000,2(1):68
6 Olayioye MA,Neve RM,Lane HA,et al.The EerbB signaling network receptor heterodimerization in development and cancer.The EMBOJ,2001, 19(13):3159
7宋建忠,苏秉忠,刘彦琦,等.EGFR基因在不同胃黏膜中表达的研究.内蒙古医学杂志,2008,40(11):1299-1301
8 Suntharalingam M,Dipetrillo T,Akerman P,et al.Cetuximad,paclitaxel, carboplatin and radiation for esophageal and gastric cancer.J Clin Oncol 2006;24 Suppl 18S:4029
9 Pinto C,Di Fabio F,Siena S,et al.Phase II study of cetuximab incombination with Folfiri in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma.Ann Oncol,2007,18(3):510-517
10 Han SW,Oh DY,Im SA,et al.PhaseⅡstudy and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.Br J Cancer,2009,100(2):298-304
11冯丹,王雅杰.EGFR家族靶向肿瘤治疗研究进展.国际肿瘤学杂志,2006,33(1):12-16
12 Rao S,Starling N,Cunningham D,et al.Phase I study of epirubicin,cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.Br J Cancer,2008,99(6):68-74
13 Schmiedel J,Blaukat A,Li S,et al.Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.Cancer Cell,2008,13(4):365-373
14 Yang XD,Jia XC,Corvalan JR,et al.Development of ABX-EGF,a fully human anti-EGF receptor monoclonal antibody for cancer therapy.Crit Rev Oncol Hematol,2001;38:17-23
15 Park JK,Lee SH,Kang JH,et al.Synergistic interaction between gefitinib (Iressa,ZD1839) and paclitaxel against human gastric carcinoma cells. Anticancer Drugs,2004,15(8):809-818
16 Rojo F,Tabernero J,Albanell J,et al.Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma.J Clin Oncol,2006,24(26):4309-4316
17 Becker JC,Müller-Tidow C,Stolte M,et al.Acetylsalicylic acid enhances antiproliferative effects of the EGFR inhibitor gefitinib in the absence of activating mutations in gastric cancer.Int J Oncol,2006,29(3):615-623
18 Dragovich T,McCoy S,Fenoglio-Preiser CM,et al.PhaseⅡtrial of erlotinib in gastroesophageal junction and gastric adenocarcinomas:SWOG 0127.J Clin Oncol,2006,24(30):4922-4927
19 Arteaga C.Targeting HER2/EGFR:A molecular approach to cancer therapy.Semin Oncol,2003,30(Suppl 7):3-14
20 Corte′s-Funes H,Rivera F,Ale′s I,et al.Phase II of trastuzumab and cisplatin in patients with advanced gastric cancer with HER-2/ neuoverexpression / amplification.J Clin Oncol,2007,15(18S):4613
21 Nicholas G,Cripps C,Au HP,et al.Early results of a trial of trastuzumab, cisplatin and docetaxel for the treatment of metastatic gastric cancer overexpressing HER-2.ESMO,2006,17(Suppl 9):316
22 Kim JW,Kim HP,Im SA,et al.The growth inhibitory effect of lapatinib,a dual inhibitor of EGFR and HER-2 tyrosine kinase,in gastric cancer cell lines.Cancer Lett,2008,272(2):296-306
23 Laman B,Lenz HJ,A phaseⅡSWOG study of GW572016(lapatinib)as first line therapy in patients with advanced or metastatic gastric cancer.J Cin Oncol,2007,25(18S):4621(abstract)
24 Hecht JR,Urba SG,Koehler M,et al.Lapatinib monotherapy in recurrent upper gastrointestinal malignancy:PhaseⅡefficacy and biomarker analyses.Proceedings 2008 Gastrointestinal Cancer Symposium Jan 25-27,Orlando:43(abstract)
25 Harlozinska A.Progress in molecular mechanisms of tumor metastasis and angiogenesis.Anticancer Res 2005;25:3327-3333
26祝学光.肿瘤分子靶向治疗进展.中华实验外科,2005,22(11):1285-1286
27 Zondor SD.Medina PJ.Bevacizumab:an angiogensis inhibitor with efficacy in colorectal and other malignancies.Ann Parmacother,2004;38(7-8): 1258-1264
28 Shah MA,Ramanathan RK,Ilson DH,et al.Multicenter phaseⅡstudy of irinotecan,cisplatin,and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.J Clin Oncol,2006,24(33): 5201-5206
29 Saitz LB,Clarke S,Diaz-Rubio E,et al.Bevacizumab in combination with oxaliplatin-based chemotherapy as first-Line therapy in metastatic colorectal cancer:A randomized phaseⅢstudy.JCO,2008,26,(12):2013
30 James AP,Thian CN,Bao LY,et al.A Phase I Study of Anti-Kinase Insert Domain-containing Receptor Antibody,IMC-1C11,in Patients with LiverMetastases from Colorectal Carcinoma.Clin Cnacer Res,2003,9:1323-1332
31 Hartman GD,Fraley ME,Bilodeau MT.Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents.Expert Opin Investig Drugs,2002,11(6):737-745
32 Arao T,Yanagihara K,Takigahira M,et al.ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model.Int J Cancer,2006,118(2):483-489
33 Tokuyama J,Kubota T,Saikawa Y,et al.Tyrosine kinase inhibitor SU6688 inhibits peritoneal dissemination of gastric cancer via suppresion of tumor angiogenesis.Anticancer Res,2005;25:17-22
34 Nomura H,Sato H,Seiki M,et al.Expression of membrane-type matrix metalloproteinase in human gastric carcinomas.Cancer Res 1995; 55:3263-3266
35 Honda M,Mori M,Ueo H,et al.Matrix metalloproteinase-7 expression in gastric carcinoma.Cut 1996;39:444-448
36 Apte SS,Olsen BR,Murphy G.The gene structure of tissue inhibitor of metalloproteinases and its inhibitory activities defene the distinct TIMP gene family.J Biol Chem,1995,270:14313
37曾仲综述,韩本立审阅.基质金属蛋白酶组织抑制剂的生物学功能.国外医学,分子生物学分册,2000,22(2):84-87
38 Kruger A,Sanchez-Sweatman OH,Martin DC,et al.Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line.Oncogene,1998,16(18):2419-2423
39 Kimata M,Otani Y,Kubota T,et al.Matrix metalloproteinase inhibitor,marimastat,decreases peritoneal spread of gastric carcinoma in nude mice.Jpn J Cancer Res,2002,93:834-841
40 Bramhall SR,Hallissey MT,Whiting J,et al.Marimastat as maintenance therapy for patients with advanced gastric cancer:a randomised trial.Br J Cancer,2002,86:1864-1870
41 Malumbres M.Preclinical models for cell cycle-targeted therapies.Adv Exp Med Biol 2006;587:139-147
42 Shapiro GI.Cyclin-dependent kinase pathways as targets for cancer treatment.J Clin Oncol 2006;24:1770-1783
43 Yamasaki L,Pagano M.Cell cycle,proteolysis and cancer.Curr Opin Cell Biol 2004;16:623-628
44 Schwartz GK,Ilson D,Saltz L,et al.Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma.J Clin Oncol,2001,19:1985-1992
45 Shah MA,Kortmansky J,Gonen M,et al.PhaseⅠstudy of weekly irinotecan (cpt),cisplatin(cis) and flavopiridol (f).Procam socclin oncol,2004,23:319
46 Zhao XH,Gu SZ,Tian HG,Quan P,Pan BR.Clinical significance of expression of apoptotic signal progress in gastric carcinoma tissue.World J.Gastroenterol 2005;11:3846-3849
47 Ocean AJ,Sehnoll-Sussman F,Chen XE,et al.Recent results of phaseⅡstudy of PS-341(bortezomib) with or without irinotecan in patients(pts) with advanced gastric adenocarcinomas(AGA).Gastrointest Cancers Symposium,2007:45(abstract)
48陈龙邦,刘福坤.循证肿瘤治疗学.郑州:郑州大学出版社,2004:229-329
1 Tsujitani S,Oka S,Suzuki K,et al.Prognosis factors in patients with advanced gastric cancer treated by noncurative resection:a multivariate analysis.Hepatogastroenterology,2001,48:1504
2 Hartgrink HH,Putter H,Klein Kranenbarg E,et al.Value of palliative resection in gastric cancer.Br J Surg,2002,89(11):1438
3 Hanazaki K,Sodeyama H,Mochizuki Y,et al.Palliative gastrectomy for advanced gastric cancer.Hepatogastroenterology,2001,48:285
4 Bonenkamp JJ,Sasako M,Hermans J,et al.Tumor load and surgical palliation in gastric cancer. Hepatogastroenterology,2001,48:1219
5 Yamaguchi K, TadaM, HorikoshiN, et al. Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer. Gastric Cancer, 2002, 5(2):90-95
6 Hong Ys, Song SY,Lee SI, et al. A phaseⅡtrial of capecitabine in previously untreated patients with advanced and /or mestastic ganstric cancer. Ann Oncol,2004,15:1344-1347
7 Thuss-Patience PC,Kretzschmar A,Dogan Y,et al.Capecitabine and docetaxel for advanced gastric cancer.J Clin Oncol 2006;24:4068
8余宏迢,周际昌,余子豪.胃癌.见:谷铣之主编.现代肿瘤学.北京:北京医科大学中国协和医科大学联合出版社,1993:435
9万德森.结肠癌辅助化疗的过去、现在和将来.临床肿瘤学现状,2006,3(2):12-13
10林云笑,黄活勋,潘岐作.单药希罗达治疗晚期乳腺癌和结直肠癌疗效观察.现代肿瘤医学,2005,13(2):247-248
11 Y. Kang,J. Lee,Y. Min et al.A randomized multi-center phase II trial of capecitabine (X) versus S-1 (S) as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement),2007:4546
12 Mahtani RL, Macdonald JS.Synergy between cetuximaband chemotherapy in tumors of the gastrointestinal tract.Oncologist,2008,13(1):39- 50
13 Shah MA,Ramanathan RK,Ilson DH,et al.Multicenter phaseⅡstudy of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.J Clin Oncol,2006,24(33): 5201-5206
14 CLARDIELLO F,TORTORA G.EGFR antagonists in cancer treatment.N Engl J Med,2008,358(11):1160-1174
15 Giuliani C, Napoitano G, Mastio A, et al. Thymosin2alpha1 regulates MHC class I expression in FRTL25 cells at transcrip tional level. Eur J Immunol, 2000,30(3):778-786
16 Hamuro J. Anticancer immunotherapywith perorally effective lentinan. Gan To Kagaku Ryoho,2005,32(8):1209-1215
17赵兴.参芪扶正注射液减轻肿瘤放化疗毒副反应的临床观察.中国中西医结合杂志,2004,24(9):857-858
2 Parkin DM,Bray FI,Devesa SS.Cancer burden in the year 2000.The global picture.Eur J Cancer,2001,37(Suppl 8):S4-S66
3詹友庆,李威,孙晓卫,等胃癌外科治疗的远期疗效研究.中华外科杂志, 2005,43(17):1109
4 MU FSON RA.Tumor antigen targets and tumor immunotherapy.Front Biosci,2006,11:337-343
5 Sako Y,Minoghchi S,Yanagida T.Single-molecule imaging of EGFR signaling on the surface of living cells.Nat Cell Biol,2000,2(1):68
6 Olayioye MA,Neve RM,Lane HA,et al.The EerbB signaling network receptor heterodimerization in development and cancer.The EMBOJ,2001, 19(13):3159
7宋建忠,苏秉忠,刘彦琦,等.EGFR基因在不同胃黏膜中表达的研究.内蒙古医学杂志,2008,40(11):1299-1301
8 Suntharalingam M,Dipetrillo T,Akerman P,et al.Cetuximad,paclitaxel, carboplatin and radiation for esophageal and gastric cancer.J Clin Oncol 2006;24 Suppl 18S:4029
9 Pinto C,Di Fabio F,Siena S,et al.Phase II study of cetuximab incombination with Folfiri in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma.Ann Oncol,2007,18(3):510-517
10 Han SW,Oh DY,Im SA,et al.PhaseⅡstudy and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.Br J Cancer,2009,100(2):298-304
11冯丹,王雅杰.EGFR家族靶向肿瘤治疗研究进展.国际肿瘤学杂志,2006,33(1):12-16
12 Rao S,Starling N,Cunningham D,et al.Phase I study of epirubicin,cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.Br J Cancer,2008,99(6):68-74
13 Schmiedel J,Blaukat A,Li S,et al.Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.Cancer Cell,2008,13(4):365-373
14 Yang XD,Jia XC,Corvalan JR,et al.Development of ABX-EGF,a fully human anti-EGF receptor monoclonal antibody for cancer therapy.Crit Rev Oncol Hematol,2001;38:17-23
15 Park JK,Lee SH,Kang JH,et al.Synergistic interaction between gefitinib (Iressa,ZD1839) and paclitaxel against human gastric carcinoma cells. Anticancer Drugs,2004,15(8):809-818
16 Rojo F,Tabernero J,Albanell J,et al.Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma.J Clin Oncol,2006,24(26):4309-4316
17 Becker JC,Müller-Tidow C,Stolte M,et al.Acetylsalicylic acid enhances antiproliferative effects of the EGFR inhibitor gefitinib in the absence of activating mutations in gastric cancer.Int J Oncol,2006,29(3):615-623
18 Dragovich T,McCoy S,Fenoglio-Preiser CM,et al.PhaseⅡtrial of erlotinib in gastroesophageal junction and gastric adenocarcinomas:SWOG 0127.J Clin Oncol,2006,24(30):4922-4927
19 Arteaga C.Targeting HER2/EGFR:A molecular approach to cancer therapy.Semin Oncol,2003,30(Suppl 7):3-14
20 Corte′s-Funes H,Rivera F,Ale′s I,et al.Phase II of trastuzumab and cisplatin in patients with advanced gastric cancer with HER-2/ neuoverexpression / amplification.J Clin Oncol,2007,15(18S):4613
21 Nicholas G,Cripps C,Au HP,et al.Early results of a trial of trastuzumab, cisplatin and docetaxel for the treatment of metastatic gastric cancer overexpressing HER-2.ESMO,2006,17(Suppl 9):316
22 Kim JW,Kim HP,Im SA,et al.The growth inhibitory effect of lapatinib,a dual inhibitor of EGFR and HER-2 tyrosine kinase,in gastric cancer cell lines.Cancer Lett,2008,272(2):296-306
23 Laman B,Lenz HJ,A phaseⅡSWOG study of GW572016(lapatinib)as first line therapy in patients with advanced or metastatic gastric cancer.J Cin Oncol,2007,25(18S):4621(abstract)
24 Hecht JR,Urba SG,Koehler M,et al.Lapatinib monotherapy in recurrent upper gastrointestinal malignancy:PhaseⅡefficacy and biomarker analyses.Proceedings 2008 Gastrointestinal Cancer Symposium Jan 25-27,Orlando:43(abstract)
25 Harlozinska A.Progress in molecular mechanisms of tumor metastasis and angiogenesis.Anticancer Res 2005;25:3327-3333
26祝学光.肿瘤分子靶向治疗进展.中华实验外科,2005,22(11):1285-1286
27 Zondor SD.Medina PJ.Bevacizumab:an angiogensis inhibitor with efficacy in colorectal and other malignancies.Ann Parmacother,2004;38(7-8): 1258-1264
28 Shah MA,Ramanathan RK,Ilson DH,et al.Multicenter phaseⅡstudy of irinotecan,cisplatin,and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.J Clin Oncol,2006,24(33): 5201-5206
29 Saitz LB,Clarke S,Diaz-Rubio E,et al.Bevacizumab in combination with oxaliplatin-based chemotherapy as first-Line therapy in metastatic colorectal cancer:A randomized phaseⅢstudy.JCO,2008,26,(12):2013
30 James AP,Thian CN,Bao LY,et al.A Phase I Study of Anti-Kinase Insert Domain-containing Receptor Antibody,IMC-1C11,in Patients with LiverMetastases from Colorectal Carcinoma.Clin Cnacer Res,2003,9:1323-1332
31 Hartman GD,Fraley ME,Bilodeau MT.Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents.Expert Opin Investig Drugs,2002,11(6):737-745
32 Arao T,Yanagihara K,Takigahira M,et al.ZD6474 inhibits tumor growth and intraperitoneal dissemination in a highly metastatic orthotopic gastric cancer model.Int J Cancer,2006,118(2):483-489
33 Tokuyama J,Kubota T,Saikawa Y,et al.Tyrosine kinase inhibitor SU6688 inhibits peritoneal dissemination of gastric cancer via suppresion of tumor angiogenesis.Anticancer Res,2005;25:17-22
34 Nomura H,Sato H,Seiki M,et al.Expression of membrane-type matrix metalloproteinase in human gastric carcinomas.Cancer Res 1995; 55:3263-3266
35 Honda M,Mori M,Ueo H,et al.Matrix metalloproteinase-7 expression in gastric carcinoma.Cut 1996;39:444-448
36 Apte SS,Olsen BR,Murphy G.The gene structure of tissue inhibitor of metalloproteinases and its inhibitory activities defene the distinct TIMP gene family.J Biol Chem,1995,270:14313
37曾仲综述,韩本立审阅.基质金属蛋白酶组织抑制剂的生物学功能.国外医学,分子生物学分册,2000,22(2):84-87
38 Kruger A,Sanchez-Sweatman OH,Martin DC,et al.Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line.Oncogene,1998,16(18):2419-2423
39 Kimata M,Otani Y,Kubota T,et al.Matrix metalloproteinase inhibitor,marimastat,decreases peritoneal spread of gastric carcinoma in nude mice.Jpn J Cancer Res,2002,93:834-841
40 Bramhall SR,Hallissey MT,Whiting J,et al.Marimastat as maintenance therapy for patients with advanced gastric cancer:a randomised trial.Br J Cancer,2002,86:1864-1870
41 Malumbres M.Preclinical models for cell cycle-targeted therapies.Adv Exp Med Biol 2006;587:139-147
42 Shapiro GI.Cyclin-dependent kinase pathways as targets for cancer treatment.J Clin Oncol 2006;24:1770-1783
43 Yamasaki L,Pagano M.Cell cycle,proteolysis and cancer.Curr Opin Cell Biol 2004;16:623-628
44 Schwartz GK,Ilson D,Saltz L,et al.Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma.J Clin Oncol,2001,19:1985-1992
45 Shah MA,Kortmansky J,Gonen M,et al.PhaseⅠstudy of weekly irinotecan (cpt),cisplatin(cis) and flavopiridol (f).Procam socclin oncol,2004,23:319
46 Zhao XH,Gu SZ,Tian HG,Quan P,Pan BR.Clinical significance of expression of apoptotic signal progress in gastric carcinoma tissue.World J.Gastroenterol 2005;11:3846-3849
47 Ocean AJ,Sehnoll-Sussman F,Chen XE,et al.Recent results of phaseⅡstudy of PS-341(bortezomib) with or without irinotecan in patients(pts) with advanced gastric adenocarcinomas(AGA).Gastrointest Cancers Symposium,2007:45(abstract)
48陈龙邦,刘福坤.循证肿瘤治疗学.郑州:郑州大学出版社,2004:229-329
1 Tsujitani S,Oka S,Suzuki K,et al.Prognosis factors in patients with advanced gastric cancer treated by noncurative resection:a multivariate analysis.Hepatogastroenterology,2001,48:1504
2 Hartgrink HH,Putter H,Klein Kranenbarg E,et al.Value of palliative resection in gastric cancer.Br J Surg,2002,89(11):1438
3 Hanazaki K,Sodeyama H,Mochizuki Y,et al.Palliative gastrectomy for advanced gastric cancer.Hepatogastroenterology,2001,48:285
4 Bonenkamp JJ,Sasako M,Hermans J,et al.Tumor load and surgical palliation in gastric cancer. Hepatogastroenterology,2001,48:1219
5 Yamaguchi K, TadaM, HorikoshiN, et al. Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer. Gastric Cancer, 2002, 5(2):90-95
6 Hong Ys, Song SY,Lee SI, et al. A phaseⅡtrial of capecitabine in previously untreated patients with advanced and /or mestastic ganstric cancer. Ann Oncol,2004,15:1344-1347
7 Thuss-Patience PC,Kretzschmar A,Dogan Y,et al.Capecitabine and docetaxel for advanced gastric cancer.J Clin Oncol 2006;24:4068
8余宏迢,周际昌,余子豪.胃癌.见:谷铣之主编.现代肿瘤学.北京:北京医科大学中国协和医科大学联合出版社,1993:435
9万德森.结肠癌辅助化疗的过去、现在和将来.临床肿瘤学现状,2006,3(2):12-13
10林云笑,黄活勋,潘岐作.单药希罗达治疗晚期乳腺癌和结直肠癌疗效观察.现代肿瘤医学,2005,13(2):247-248
11 Y. Kang,J. Lee,Y. Min et al.A randomized multi-center phase II trial of capecitabine (X) versus S-1 (S) as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement),2007:4546
12 Mahtani RL, Macdonald JS.Synergy between cetuximaband chemotherapy in tumors of the gastrointestinal tract.Oncologist,2008,13(1):39- 50
13 Shah MA,Ramanathan RK,Ilson DH,et al.Multicenter phaseⅡstudy of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.J Clin Oncol,2006,24(33): 5201-5206
14 CLARDIELLO F,TORTORA G.EGFR antagonists in cancer treatment.N Engl J Med,2008,358(11):1160-1174
15 Giuliani C, Napoitano G, Mastio A, et al. Thymosin2alpha1 regulates MHC class I expression in FRTL25 cells at transcrip tional level. Eur J Immunol, 2000,30(3):778-786
16 Hamuro J. Anticancer immunotherapywith perorally effective lentinan. Gan To Kagaku Ryoho,2005,32(8):1209-1215
17赵兴.参芪扶正注射液减轻肿瘤放化疗毒副反应的临床观察.中国中西医结合杂志,2004,24(9):857-858