Molecularly targeted therapies in advanced gastric cancer

Minerva Gastroenterologica e Dietologica

Volumn 57, Issue 1, 2011, Pages 75-88

  Janjigian, Y Y ^a   Shah, M A ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Molecular targeted therapy; Neoplasm metastasis; Stomach neoplasms

Indexed keywords

ANTINEOPLASTIC AGENT; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CETUXIMAB; CISPLATIN; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; EPIRUBICIN; ERLOTINIB; FLAVOPIRIDOL; FLUOROURACIL; FOLFOX; FORETINIB; GEFITINIB; GEMCITABINE; IRINOTECAN; LAPATINIB; MATUZUMAB; OXALIPLATIN; PACLITAXEL; PANITUMUMAB; SOMATOMEDIN C RECEPTOR; SORAFENIB; SUNITINIB; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN;

ADD ON THERAPY; ADVANCED CANCER; ANAPHYLAXIS; CANCER CLASSIFICATION; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CHRONIC GASTRITIS; CLINICAL TRIAL (TOPIC); CONTINUOUS INFUSION; DIARRHEA; DISEASE SEVERITY; DRUG EFFICACY; DRUG RESISTANCE; DRUG SAFETY; DRUG TARGETING; ENZYME ACTIVITY; ESOPHAGUS CANCER; FLUORESCENCE IN SITU HYBRIDIZATION; GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; GASTROESOPHAGEAL REFLUX; GENE AMPLIFICATION; GENE MUTATION; HELICOBACTER PYLORI; HUMAN; IMMUNOHISTOCHEMISTRY; LIGAND BINDING; LOWER ESOPHAGUS SPHINCTER; LUNG NON SMALL CELL CANCER; MOLECULARLY TARGETED THERAPY; MULTICENTER STUDY (TOPIC); NEUTROPENIA; NONHUMAN; OVERALL SURVIVAL; PERITONEUM METASTASIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGNOSIS; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; SKIN TOXICITY; STOMACH ADENOCARCINOMA; STOMACH CANCER; STOMACH HEMORRHAGE; STOMACH PERFORATION; THROMBOEMBOLISM; TREATMENT RESPONSE; TUMOR VOLUME; UNSPECIFIED SIDE EFFECT;

ANGIOGENESIS INHIBITORS; CLINICAL TRIALS AS TOPIC; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM STAGING; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; STOMACH NEOPLASMS; TREATMENT OUTCOME; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 79957633459     PISSN: 00264776     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (128)

1. Garcia M, Jemal A, Ward EM, Center MM, Hao Y, Siegel RL. Global cancer facts & figures 2007. Atlanta, GA: American Cancer Society.
2. Kamangar F, Dawsey SM, Blaser MJ, Perez-Perez GI, Pietinen P, Newschaffer CJ, et al. Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity. Journal of the National Cancer Institute 2006;98:1445-52. (Pubitemid 44605589)
3. Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P et al. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: A randomized phase II trial of the Swiss group for clinical cancer research. J Clin Oncol 2007;25:3217-23. (Pubitemid 47325604)
4. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C 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 V25 study group. J Clin Oncol 2006;24:4991-7. (Pubitemid 46631401)
5. Shah MA, Stoller R, Shibata S. Random assignment multicenter phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF) versus DCF with growth factor support (GCSF) in metastatic gastroesophageal adenocarcinoma (GE). Presented at the 2010 Gastrointestinal Cancers Symposium; January 22-24, 2010; Orlando, Florida.
6. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. Engl J Med 2008;358:36-46.
7. Tay ST, Leong SH, Yu K, Aggarwal A, Tan SY, Lee CH, et al. A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes. Cancer Res 2003;63:3309-16. (Pubitemid 36735888)
8. Ueda S, Hironaka S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Combination chemotherapy with irinotecan and cisplatin in pretreated patients with unresectable or recurrent gastric cancer. Gastric Cancer 2006;9:203-7. (Pubitemid 44426894)
9. Shah MA, Kelsen DP. Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease. J Natl Compr Canc Netw 2010;8:437-47.
10. Lauren P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand 1965;64:31-49.
11. Carneiro F, Huntsman DG, Smyrk TC, Owen DA, Seruca R, Pharoah P et al. Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and it's implications for patient screening. J Pathol 2004;203:681-7. (Pubitemid 38714105)
12. Yuo WC, Blot WJ, Li JY, Chang YS, Jin ML, Kneller R et al. Precancerous gastric lesions in a population at high risk of stomach cancer. Cancer Res 1993;53:1317-21.
13. Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G et al. Gastric precancerous process in a high risk population: cross-sectional studies. Cancer Res 1990;50:4731-6. (Pubitemid 20230421)
14. Anderson WF, Camargo MC, Fraumeni Jr JF, Correa P, Rosenberg PS, Rabkin CS. Age-specific trends in incidence of noncardia gastric cancer in US adults. JAMA 2010;303:1723-8.
15. Steevens J, Botterweck AA, Dirx MJ, van den Brandt PA, Schouten LJ. Trends in incidence of oesophageal and stomach cancer subtypes in Europe. Eur J Gastroenterol Hepatol;22:669-78.
16. Blot WJ, DeVesa SS, Kneller RW, Fraumeni JF. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991:1287-9.
17. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12:354-62.
18. Marrelli D, Roviello F, de Manzoni G, Morgagni P, Di Leo A, Saragoni L et al. Different patterns of recurrence in gastric cancer depending on Lauren's histologic type: longitudinal study. World J Surg 2002;26:1160-5. (Pubitemid 36920276)
19. Sakaguchi T, Watanabe A, Sawada H, Yamada Y, Tatsumi M, Fujimoto H et al. Characteristics and clinical outcome of proximal-third gastric cancer. J Am Coll Surg 1998;187:352-7. (Pubitemid 28467609)
20. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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. Lancet 2010;376:687-97.
21. Hofmann M, Stoss O, Shi D, BÃ1/4ttner R, Van De Vijver M, Kim W et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 2008;52:797-805.
22. Tafe LJ, Janjigian YY, Hameed M, Ladanyi M, Tang L, Hicks JB et al. HER2 testing in gastric cancer: correlation between IHC and FISH. Accepted to Archives of Pathology and Laboratory Medicine 2010.
23. Hudis CA. Trastuzumab - Mechanism of action and use in clinical practice. New Engl J Med 2007;357:39-51.
24. Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res 1991;51:1034-8.
25. Uchino S, Tsuda H, Maruyama K, Kinoshita T, Sasako M, Saito T et al. Overexpression of c-erbB-2 protein in gastric cancer: Its correlation with longterm survival of patients. Cancer 1993;72:3179-84.
26. Mizutani T, Onda M, Tokunaga A, Yamanaka N, Sugisaki Y Relationship of C-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer. Cancer 1993;72:2083-8. (Pubitemid 23280130)
27. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J et al. The prognostic significance of amplification and overexpression of c- met and c-erb B-2 in human gastric carcinomas. Cancer 1999;85:1894-902.
28. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006;51:1371-9. (Pubitemid 44315804)
29. Bang Y, Chung H, Xu J. Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol 2009;27(15 S).
30. Hofman M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W et al. Assessment of a Her2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797-805.
31. Devesa SS, Fraumeni JF. The rising incidence of gastric cardia cancer. Journal of the National Cancer Institute 1999;91:747-9.
32. Osipo C, Patel P, Rizzo P, Clementz AG, Hao L, Golde TE et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a [gamma]-secretase inhibitor. Oncogene 2008;27:5019-32.
33. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007;12:395-402.
34. Eichhorn PJA, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W et al. Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235. Cancer Res 2008;68:9221-30.
35. Nagata Y, Un K-H, Zhou X, Tan M, Esteva FJ, Sahin AA et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004;6:117-27.
36. Nahta R, Yuan LXH, Zhang B, Kobayashi R, Esteva FJ. Insulin-like Growth Factor-I Receptor/Human Epidermal Growth Factor Receptor 2 Heterodimerization Contributes to Trastuzumab Resistance of Breast Cancer Cells. Cancer Res 2005;65:11118-28.
37. Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M. Insulin-like growth factor-i receptor signaling and resistance to trastuzumab (herceptin). J Natl Cancer Inst 2001;93:1852-57.
38. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to Anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007;99:628-38.
39. Gomez HL, Doval DC, Chavez MA, Ang PC-S, Aziz Z, Nag S et al. Efficacy and safety of lapatinib as firstline therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 2008;26:2999-3005.
40. O'Shaughnessy J, Blackwell KL, Burstein H, Storniolo AM, Sledge G, Baselga J et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. J Clin Oncol (Meeting Abstracts) 2008;26(15-suppl):1015-.
41. Iqbal S, Goldman HJL, Fenoglio-Preiser M, Blanke C. S0413: a phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 4621
42. Lapatinib monotherapy in recurrent upper gastrointestinal malignancy: Phase II efficacy and biomarker analyse. Proc GI ASCO 2008, vol. 43 abstr; 2008.
43. Galsky M, Von Hoff D, Neubauer M. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. J Clin Oncol 2009;27:3541.
44. Interim safety analysis from TYTAN: A phase III Asian study of lapatinib in combination with paclitaxel as second-line therapy in gastric cancer. J Clin Oncol 2010;28:15s.
45. Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995;1:1311-8.
46. Baselga J, Norton L, Masui H, Pandiella A, Coplan K, Miller Jr WH et al. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. Journal of the National Cancer Institute 1993;85:1327-33.
47. Mendelsohn J, Baselga J. Epidermal growth factor receptor targeting in cancer. Sem Oncol 2006;33:369-85.
48. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341-54.
49. Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Canc 2007;120:781-7.
50. Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nature Reviews Cancer 2006;6:714-27.
51. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New Engl J Med 2004;351:337-45.
52. Adams R, Maughan T. Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer. Expert Rev Anticancer Ther 2007;7:503-18.
53. Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005;23:1803-10.
54. Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 2007;18:510-17.
55. Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Rojas Llimpe FL. Cetuximab in combination with cisplatin and docetaxel as first-line treatment in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Italian phase II DOCETUX study). J Clin Oncol (Meeting Abstracts) 2008;26:4575.
56. Kanzler S, Trarbach T, Seufferlein T. Cetuximab with irinotecan/folinic acid/5-FU as first-line treatment in advanced gastric cancer: A nonrandomized multicenter AIO phase II study. J Clin Oncol 2009;27:4534.
57. Lordick F, Lorenzen S, Hegewisch-Becker S. Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group. J Clin Oncol 2007;25(18 S):4526.
58. Yeh K, Hsu C. Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer. J Clin Oncol 2009;27:4567.
59. A phase II study of cetuximab with cisplatin and capecitabine as first-line treatment in advanced gastric cancer.; 2009.
60. Woell E, Greil R, Eisterer W. Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT). J Clin Oncol 2009;27:4538.
61. Moutinho C, Mateus AR, Milanezi F, Carneiro F, Seruca R, Suriano G. Epidermal growth factor receptor structural alterations in gastric cancer. BMC Cancer 2008;8.
62. Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz H-J, et al. Cetuximab as Second-Line Therapy in Patients with Metastatic Esophageal Adenocarcinoma: A Phase II Southwest Oncology Group Study (S0415). J Thoracic Oncol 2010;5:1472-6.
63. ATTAX2: Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophago-gastric cancer-Final results of a multicentre phase II trial by the AGITG. J Clin Oncol 2008;26 (May 20 suppl; abstr 15554).
64. Schønnemann KR, Bjerregaard JK, Jensen HA, Vestermark LW, Højberg L, Pfeiffer P. Biweekly cetuximab and irinotecan as second-line therapy to patients with platinium-resistant gastroesophageal cancer.; 2009 Gastrointestinal Cancers Symposium
65. Rao S, Starling N, Cunningham D, Sumpter K, Gilligan D, Ruhstaller T et al. Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophagogastric cancer: a randomised, multicentre open-label phase II study. Ann Oncol 2010;21:2213-9.
66. Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS et al. Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 2009;100:298-304.
67. Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, Meijer GA, Vervenne WL, Richel DJ et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol 2006;24:1612-9.
68. Kim YJ, Kim MA, Im SA, Kim TM, Kim DW, Yang HK et al. Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer. Cancer Invest 2008;26:152-8.
69. Galizia G, Lieto E, Orditura M, Castellano P, Mura A, Imperatore V et al. Prognostic Biomarkers and Targeted Therapy in Gastric Cancer: Reply. World J Surg 2008;32:1227-9.
70. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39.
71. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500.
72. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306-11.
73. Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF et al. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol 2006;24:4922-7.
74. Eroglu A, Demirci S, Ayyildiz A, Kocaoglu H, Akbulut H, Akgul H et al. Serum concentrations of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer. Br J Cancer 1999;80:1630-4.
75. Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C et al. Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery. Ann Surg 2002;236:37-42.
76. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 1996;77:858-63.
77. Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Yanoma S et al. Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. Cancer Lett 2000;153:7-12.
78. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl J Med 2004;350:2335-42.
79. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25:1539-44.
80. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New Engl J Med 2006;355:2542-50.
81. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Archer L et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic ren
82. Escudier B, Bellmunt J, Négrier S, Bajetta E, Melichar B, Bracarda S et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010;28:2144-50.
83. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27:740-45.
84. Shah MA, Ilson D, Kelsen DP. Thromboembolic events in gastric cancer: High incidence in patients receiving irinotecan- and bevacizumab-based therapy. J Clin Oncol 2005;23:2574-76.
85. Van Cutsem E, Kang K, Chung H, Shen L, Sawaki A, Lordick F et al. Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). American Society of Clinial Oncology, Annual Proceedings, Orlando, FL, USA. May 29th - June 2nd 2009:Abstract #LBA 4509.
86. Shah M. Phase II Study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol 2010 [Epub ahead of print].
87. Enzinger PC, Ryan DP, Regan EM. Phase II trial of , docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer. J Clin Oncol 2008;26(15 SUPPL.):abstract 4552.
88. El-Rayes B, Patel B, Zalupski M. A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer, American Society of Clinical Oncology. Orlando, FL. J Clin Oncol 2009;27:4563.
89. AVAGAST: A randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC). J Clin Oncol 28:18s, 2010 (suppl; abstr LBA4007) 2010.
90. th ESMO Congress, October 8-12 2010, Milan, Italy 2010.
91. Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol;11:1172-83.
92. Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, Benson AB, 3rd. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol 2010;28:2947-51.
93. Kim C, Lee JL, Choi YH, Kang BW, Ryu MH, Chang HM et al. Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a firstline treatment in patients with advanced gastric cancer. Invest New Drugs 2010. [Epub ahead of print].
94. Bang YJ, Kang YK, Kang WK, Boku N, Chung HC, Chen JS et al. Phase II study of sunitinib as secondline treatment for advanced gastric cancer. Invest New Drugs 2010 . [Epub ahead of print].
95. Smolen GA, Sordella R, Muir B, Mohapatra G, Barmettler A, Archibald H et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA665752. Proc Natl Acad Sci U S A 2006;103:2316-21.
96. Kuniyasu H, Yasui W, Kitadai Y, Yokozaki H, Ito H, Tahara E. Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem Biophys Res Commun 1992;189:227-32.
97. Seruca R, Suijkerbuijk RF, Gartner F, Criado B, Veiga I, Olde-Weghuis D et al. Increasing levels of MYC and MET co-amplification during tumor progression of a case of gastric cancer. Cancer Genet Cytogenet 1995;82:140-5.
98. Tsujimoto H, Sugihara H, Hagiwara A, Hattori T. Amplification of growth factor receptor genes and DNA ploidy pattern in the progression of gastric cancer. Virchows Arch 1997;431:383-9.
99. Nessling M, Solinas-Toldo S, Wilgenbus KK, Borchard F, Lichter P. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2. Genes Chromosomes Cancer 1998;23:307-16.
100. Sakakura C, Mori T, Sakabe T, Ariyama Y, Shinomiya T, Date K et al. Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization. Genes Chrom Cancer 1999;24:299-305.
101. Janjigian YY TL, Daniel G, Coit DG, Kelsen DP, Francone TD, Weiser MR et al. MET expression and amplification in patients with localized gastric cancer. submitted to Cancer Epidemiol Biomarkers Prevention 2010 (Epub ahead of print].
102. Dent DM. Cancer surgery: Why some survival benefits may be artefactual. Br J Surgery 1998;85:433-34.
103. Shiu MH, Moore E, Sanders M, Huvos A, Freedman B, Goodbold J et al. Influence of the extent of resection on survival after curative treatment of gastric carcinoma. A retrospective multivariate analysis. Arch Surg 1987;122:1347-51.
104. Siewert JR, Bottcher K, Roder JD, Busch R, Hermanek P, Meyer HJ. Prognostic relevance of systematic lymph node dissection in gastric carcinoma. Br J Surg 1993;80:1015-8.
105. Faycal J, Bessaguet C, Nousbaum JB, Cauvin JM, Cholet F, Bideau K, et al. Epidemiology and long term survival of gastric carcinoma in the French district of FinistÃ̈re between 1984 and 1995. Gastroenterol Clin Biolog 2005;29:23-32.
106. Steinberg ML, Hwang BJ, Tang L, Shah MA. E-cadherin gene alterations in gastric cancers in different ethnic populations. Ethnic Disease 2008;18(2 SUPPL. 2).
107. Zhang J, Dou C, Song Y, Ji C, Gu S, Xie Y et al. Polymorphisms of tumor necrosis factor-alpha are associated with increased susceptibility to gastric cancer: A meta-analysis. J Hum Genet 2008;53:479-89.
108. Zhou Y, Li N, Zhuang W, Liu GJ, Wu TX, Yao X et al. Interleukin-10-1082 promoter polymorphism associated with gastric cancer among Asians. Eur J Cancer 2008;44:2648-54.
109. Assessment of two dosing schedules of GSK1363089 (GSK089), a dual MET/VEGFR2 inhibitor, in metastatic gastric cancer (GC): Interim results of a multicenter phase II study. J Clin Oncol 2009;27:15s, 2009 (suppl; abstr 4502).
110. Motwani M, Delohery TM, Schwartz GK. Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. Clin Cancer Res 1999;5:1876-83.
111. Motwani M, Jung C, Sirotnak FM, She Y, Shah MA, Gonen M et al. Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in HCT-116 colon cancer monolayers and xenografts. Clin Cancer Res 2001;7:4209-19.
112. Shah MA, Schwartz GK. Cell Cycle mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res 2001;7:2168-81.
113. Shah MA, Kortmansky J, Motwani M, Drobjnak M, Gonen M, Yi S et al. A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol. Clin Cancer Res 2005;11:3836-45.
114. Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 2005;23:9408-21.
115. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-smallcell lung cancer: a phase III trial - INTACT1. J Clin Onc 2004;22:777-84.
116. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-smallcell lung cancer: a phase III trial - INTACT2. J Clin Onc 2004;22:785-94.
117. Solit DB, She Y, Lobo J, Kris M, Scher HI, Rosen N et al. Pulsatile administration of the epidermal growth factor receptor inhibitor Gefitinib is significantly more effective than continuous dosing for sensitizing tumors to paclitaxel. Clin Cancer Res 2005;11:1983-9.
118. Motwani M, Shah MA, Schwartz GK. p53 is a critical element for response to sequential SN-38 (SN) and flavopiridol (F): In vitro studies and clinical correlates. Proc Amer Soc Clin Oncol 2004;45:567.
119. Ambrosini G, Seelman SL, Qin LX, Schwartz GK. The cyclin-dependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase I poisons by suppressing Rad51 expression in a p53-dependent manner. Cancer Res 2008;68:2312-20.
120. Ku G, Shah M, Tang L. 2008;54.
121. Ferry DR, Anderson M, Beddard K, Tomlinson S, Atherfold P, Obszynska J et al. A phase ii study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res 2007;13:5869-75.
122. Tew W, Shah M, Schwartz G, Kelsen D, Ilson D. Phase II trial of erlotonib for second-line treatment in advanced esophageal cancer. In: Proc GI ASCO 2005;5 abstr.
123. Shah MA, Ramanathan RK, Ilson DH, Levnor A, D'Adamo D, O'Reilly E et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 2006;24:5201-06.
124. Enzinger PC, Ryan DP, Regan EM. Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer. J Clin Oncol 2008;26(15 Suppl.):4552.
125. Enzinger PC, Yock T, Suh W. Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer. J Clin Oncol 2006;24(18 Suppl.):4064.
126. Sun W, Powell ME, O'Dwyer P. A phase II study: combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203). J Clin Oncol 2008;26(Suppl. 1):4535.
127. Kim C, Lee J, Choi Y Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer. J Clin Oncol 2009;27:4559.
128. Bang Y, Kang Y, Kang W. Sunitinib as secondline treatment for advanced gastric cancer: Preliminary results from a phase II study. J Clin Oncol 2007;25:4603.