Medical Oncology

, 30:464 | Cite as

Metastatic gastric cancer treatment: a little slow but worthy progress

Review Article

Abstract

Metastatic gastric cancer is incurable and remains one of the leading causes of cancer-related deaths around the world. Despite the significant progress in its systemic treatment, metastatic gastric cancer is still a major therapeutic challenge for oncologists. Newer chemotherapy regimens and the addition of molecularly targeted agents to chemotherapy seem to provide better clinical outcomes for patients with metastatic gastric cancer. The objective of this article is to review the current treatment approach for this formidable disease.

Keywords

Gastric cancer Chemotherapy Targeted treatment 

Notes

Conflict of interest

There is no conflict of interest in this paper

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Yalcin S. Gastric cancer in Turkey-a bridge between West and East. Gastrointest Cancer Res. 2009;3:29–32.PubMedGoogle Scholar
  3. 3.
    Wagner AD, Grothe W, Haerting J, Kleber G, et al. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Delaunoit T. Latest developments and emerging treatment options in the management of stomach cancer. Cancer Manag Res. 2011;3:257–66.PubMedCrossRefGoogle Scholar
  5. 5.
    Pozzo C, Barone C. Is there an optimal chemotherapy regimen for the treatment of advanced gastric cancer that will provide a platform for the introduction of new biological agents? Oncologist. 2008;13:794–806.PubMedCrossRefGoogle Scholar
  6. 6.
    Price TJ, Shapiro JD, Segelov E, Karapetis CS. Management of advanced gastric cancer. Expert Rev Gastroenterol Hepatol. 2012;6(2):199–209.PubMedCrossRefGoogle Scholar
  7. 7.
    Zagouri F, Papadimitriou CA, Dimopoulos MA, Pectasides D. Molecularly targeted therapies in unresectable-metastatic gastric cancer: a systematic review. Cancer Treat Rev. 2011;37:599–610.PubMedCrossRefGoogle Scholar
  8. 8.
    Lee J, Lim T, Uhm JE, Park KW, et al. Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma. Ann Oncol. 2007;18:886–91.PubMedCrossRefGoogle Scholar
  9. 9.
    Koo DH, Ryoo BY, Kim HJ, Ryu MH, et al. A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models. Cancer Chemother Pharmacol. 2011;68:913–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Kim JG, Ryoo BY, Park YH, Kim BS, et al. Prognostic factors for survival of patients with advanced gastric cancer treated with cisplatin-based chemotherapy. Cancer Chemother Pharmacol. 2008;61:301–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Chau I, Norman AR, Cunningham D, Waters JS, et al. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer–pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol. 2004;22:2395–403.PubMedCrossRefGoogle Scholar
  12. 12.
    Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the East and West. J Clin Oncol. 2006;24:2188–96.PubMedCrossRefGoogle Scholar
  13. 13.
    Ohtsu A. Diverse eastern and Western approaches to the management of gastric cancer. Gastrointest Cancer Res. 2007;1(2 Suppl):S10–5.PubMedGoogle Scholar
  14. 14.
    Ohtsu A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol. 2008;43:256–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Kang H, Kauh JS. Chemotherapy in the treatment of metastatic gastric cancer: is there a global standard? Curr Treat Options Oncol. 2011;12:96–106.PubMedCrossRefGoogle Scholar
  16. 16.
    Power DG, Kelsen DP, Shah MA. Advanced gastric cancer–slow but steady progress. Cancer Treat Rev. 2010;36:384–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Boku N, Gastrointestinal Oncology Study Group of Japan Clinical Oncology Group. Chemotherapy for metastatic disease: review from JCOG trials. Int J Clin Oncol. 2008;13:196–200.PubMedCrossRefGoogle Scholar
  18. 18.
    Boku N. Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol. 2011;41:1315–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Blum MA, Suzuki A, Taketa T, Ajani J. The role of S-1 in the treatment of gastric cancer. Gastrointest Cancer Targets Ther. 2011;1:59–67.Google Scholar
  20. 20.
    Kubota T. The role of S-1 in the treatment of gastric cancer. Br J Cancer. 2008;98:1301–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Boku N. Chemotherapy for metastatic gastric cancer in Japan. Int J Clin Oncol. 2008;13:483–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Shirasaka T. Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas. Jpn J Clin Oncol. 2009;39:2–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Chollet P, Schöffski P, Weigang-Köhler K, Schellens JH, et al. Phase II trial with S-1 in chemotherapy-naïve patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG). Eur J Cancer. 2003;39:1264–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, et al. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer. 1998;34:1715–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000;58:191–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Koizumi W, Narahara H, Hara T, Takagane A, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Boku N, Yamamoto S, Fukuda H, Shirao K, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Narahara H, Iishi H, Imamura H, Tsuburaya A, et al. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011;14:72–80.PubMedCrossRefGoogle Scholar
  29. 29.
    Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010;28:1547–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Scartozzi M, Galizia E, Verdecchia L, Berardi R, et al. Chemotherapy for advanced gastric cancer: across the years for a standard of care. Expert Opin Pharmacother. 2007;8:797–808.PubMedCrossRefGoogle Scholar
  31. 31.
    Webb A, Cunningham D, Scarffe JH, Harper P, et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997;15:261–7.PubMedGoogle Scholar
  32. 32.
    Miwa M, Ura M, Nishida M, Sawada N, et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998;34:1274–81.PubMedCrossRefGoogle Scholar
  33. 33.
    Cunningham D, Starling N, Rao S, Iveson T, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Eng J Med. 2008;358:36–46.CrossRefGoogle Scholar
  34. 34.
    Köhne CH, Catane R, Klein B, Ducreux M, et al. Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial. Br J Cancer. 2003;89:997–1001.PubMedCrossRefGoogle Scholar
  35. 35.
    Moehler M, Eimermacher A, Siebler J, Höhler T, et al. Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer. Br J Cancer. 2005;92:2122–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Dank M, Zaluski J, Barone C, Valvere V, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008;19:1450–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Nishiyama M, Wada S. Docetaxel: its role in current and future treatments for advanced gastric cancer. Gastric Cancer. 2009;12:132–41.PubMedCrossRefGoogle Scholar
  38. 38.
    Ridwelski K, Gebauer T, Fahlke J, Kröning H, et al. Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer. Ann Oncol. 2001;12:47–51.PubMedCrossRefGoogle Scholar
  39. 39.
    Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, et al. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res. 2006;12:3402–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Chun JH, Kim HK, Lee JS, Choi JY, et al. Weekly docetaxel in combination with capecitabine in patients with metastatic gastric cancer. Am J Clin Oncol. 2005;28:188–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Thuss-Patience PC, Kretzschmar A, Repp M, Kingreen D, et al. Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin, and fluorouracil for advanced gastric adenocarcinoma: a randomized phase II study. J Clin Oncol. 2005;23:494–501.PubMedCrossRefGoogle Scholar
  42. 42.
    Van Cutsem E, Van de Velde C, Roth A, Lordick F, et al. Expert opinion on management of gastric and gastro-oesophageal junction adenocarcinoma on behalf of the European Organisation for Research and Treatment of Cancer (EORTC)-gastrointestinal cancer group. Eur J Cancer. 2008;44:182–94.PubMedCrossRefGoogle Scholar
  43. 43.
    Roth AD, Maibach R, Martinelli G, Fazio N, et al. Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO). Ann Oncol. 2000;11:301–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Roth AD, Fazio N, Stupp R, Falk S, 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.PubMedCrossRefGoogle Scholar
  45. 45.
    Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, 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 Clin Oncol. 2006;24:4991–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Ajani JA, Moiseyenko VM, Tjulandin S, Majlis A, 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 Clin Oncol. 2007;25:3210–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Ajani JA. Optimizing docetaxel chemotherapy in patients with cancer of the gastric and gastroesophageal junction: evolution of the docetaxel, cisplatin, and 5-fluorouracil regimen. Cancer. 2008;113:945–55.PubMedCrossRefGoogle Scholar
  48. 48.
    Mackenzie M, Spithoff K, Jonker D. Systemic therapy for advanced gastric cancer: a clinical practice guideline. Curr Oncol. 2011;18:e202–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Ajani JA, Barthel JS, Bekaii-Saab T, Bentrem DJ, et al. Gastric Cancer. J Natl Compr Canc Netw. 2010;8:378–409.PubMedGoogle Scholar
  50. 50.
    Al-Batran SE, Atmaca A, Hegewisch-Becker S, Jaeger D, et al. Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol. 2004;22:658–63.PubMedCrossRefGoogle Scholar
  51. 51.
    De Vita F, Giuliani F, Silvestris N, Catalano G, et al. Human epidermal growth factor receptor 2 (HER2) in gastric cancer: a new therapeutic target. Cancer Treat Rev. 2010;36(suppl 3):S11–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Fornaro L, Lucchesi M, Caparello C, Vasile E, et al. Anti-HER agents in gastric cancer: from bench to bedside. Nat Rev Gastroenterol Hepatol. 2011;8:369–83.PubMedCrossRefGoogle Scholar
  53. 53.
    Hynes NE, Horsch K, Olayioye MA, Badache A. The ErbB receptor tyrosine family as signal integrators. Endocr Relat Cancer. 2001;8:151–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Barros FF, Powe DG, Ellis IO, Green AR. Understanding the HER family in breast cancer: interaction with ligands, dimerization and treatments. Histopathology. 2010;56:560–72.PubMedCrossRefGoogle Scholar
  55. 55.
    Bazley LA, Gullick WJ. The epidermal growth factor receptor family. Endocr Relat Cancer. 2005;12(Suppl 1):S17–27.PubMedCrossRefGoogle Scholar
  56. 56.
    Song HS, Do YR, Kim IH, Sohn SS, et al. Prognostic significance of immunohistochemical expression of EGFR and C-erbB-2 oncoprotein in curatively resected gastric cancer. Cancer Res Treat. 2004;36:240–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Wong H, Yau T (2012) Targeted therapy in the management of advanced gastric cancer: are we making progress in the era of personalized medicine? Oncologist (Epub ahead of print).Google Scholar
  58. 58.
    Pinto C, Di Fabio F, Siena S, Cascinu S, 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;18:510–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Lordick F, Lorenzen S, Hegewisch-Becker S, Folprecht G et al (2007) 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 25 (18S):4514 (Abstr).Google Scholar
  60. 60.
    Han SW, Oh DY, Im SA, Park SR, 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.PubMedCrossRefGoogle Scholar
  61. 61.
    Pinto C, Di Fabio F, Barone C, Siena S, et al. Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). Br J Cancer. 2009;101:1261–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Zhang X, Xu J, Shen L, Wang J et al (2009) A phase II study of cetuximab with cisplatin and capecitabine as first-line treatment in advanced gastric cancer [abstract LBA39]. Presented at the 2009 American Society of clinical Oncology Gastrointestinal Cancer Symposium, San Francisco, CA, 15–17 January 2009.Google Scholar
  63. 63.
    Yeh K, Hsu C, Hsu C, Lin C, et al. Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer. J Clin Oncol. 2009;27(15 suppl):4567.Google Scholar
  64. 64.
    Woell E, Greil R, Eisterer W, Fridrik M et al (2008) Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) [abstract 15587]. Proc Am Soc Clin Oncol 26:662s.Google Scholar
  65. 65.
    Moehler M, Mueller A, Trarbach T, Lordick F, et al. Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol. 2011;22:1358–66.PubMedCrossRefGoogle Scholar
  66. 66.
    Kim C, Lee JL, Ryu MH, Chang HM, et al. A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Invest New Drugs. 2011;29:366–73.PubMedCrossRefGoogle Scholar
  67. 67.
    Enzinger PC, Burtness B, Hollis D, Niedzwiecki D, et al. CALGB 80403/ECOG 1206: a randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. J Clin Oncol. 2010;28(suppl 15):a4006.Google Scholar
  68. 68.
    Richards DA, Kocs DM, Spira AI, McCollum AD et al (2011) Results of docetaxel plus oxaliplatin (DOCOX) with or without cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: results of a randomized phase II study. J Clin Oncol 29(suppl; abstr 4015).Google Scholar
  69. 69.
    Merck KGaA. Erbitux in combination with xeloda and cisplatin in advanced esophago-gastric cancer (EXPAND). Available from http://clinicaltrials.gov/ct2/show/NCT00678535.
  70. 70.
    Waddell TS, Chau I, Barbachano Y, Gonzalez de Castro D et al (2012) A randomized multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3). J Clin Oncol 30(suppl; abstr LBA4000).Google Scholar
  71. 71.
    Sakai K, Mori S, Kawamoto T, Taniguchi S, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst. 1986;77:1047–52.PubMedGoogle Scholar
  72. 72.
    Hicks DG, Whitney-Miller C. HER2 testing in gastric and gastroesophageal junction cancers: a new therapeutic target and diagnostic challenge. Appl Immunohistochem Mol Morphol. 2011;19:506–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Jorgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-a systematic analysis of data from the literature. J Cancer. 2012;3:137–44.PubMedCrossRefGoogle Scholar
  74. 74.
    Kaur A, Dasanu CA. Targeting the HER2 pathway for the therapy of lower esophageal and gastric adenocarcinoma. Expert Opin Pharmacother. 2011;12:2493–503.PubMedCrossRefGoogle Scholar
  75. 75.
    Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Rose JS, Bekaii-Saab TS. New developments in the treatment of metastatic gastric cancer: focus on trastuzumab. Onco Targets Ther. 2011;4:21–6.PubMedGoogle Scholar
  77. 77.
    Ngeow J, Tan IB, Choo SP. Targeted therapies in the treatment of gastric cancer. Asia Pac J Clin Oncol. 2011;7:224–35.PubMedCrossRefGoogle Scholar
  78. 78.
    Meza-Junco J, Au HJ, Sawyer MB. Critical appraisal of trastuzumab in treatment of advanced stomach cancer. Cancer Manag Res. 2011;3:57–64.PubMedCrossRefGoogle Scholar
  79. 79.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43.PubMedGoogle Scholar
  80. 80.
    Hofmann M, Stoss O, Shi D, Büttner R, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.PubMedCrossRefGoogle Scholar
  81. 81.
    Moelans CB, van Diest PJ, Milne AN, Offerhaus GJ (2011) Her-2/neu testing and therapy in gastroesophageal adenocarcinoma. Patholog Res Int 674182.Google Scholar
  82. 82.
    Lorenzen S, Lordick F. How will human epidermal growth factor receptor 2-neu data impact clinical management of gastric cancer. Curr Opin Oncol. 2011;23:396–402.PubMedCrossRefGoogle Scholar
  83. 83.
    Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, 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(9742):687–97.PubMedCrossRefGoogle Scholar
  84. 84.
    Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.PubMedCrossRefGoogle Scholar
  85. 85.
    Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol. 2009;19:329–37.PubMedCrossRefGoogle Scholar
  86. 86.
    Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–10.PubMedCrossRefGoogle Scholar
  87. 87.
    Neufeld G, Kessler O. Pro-angiogenic cytokines and their role in tumor angiogenesis. Cancer Metastasis Rev. 2006;25:373–85.PubMedCrossRefGoogle Scholar
  88. 88.
    Reinacher-Schick A, Pohl M, Schmiegel W. Drug insight: antiangiogenic therapies for gastrointestinal cancers–focus on monoclonal antibodies. Nat Clin Pract Gastroenterol Hepatol. 2008;5:250–67.PubMedCrossRefGoogle Scholar
  89. 89.
    Lieto E, Ferraraccio F, Orditura M, Castellano P, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 2008;15:69–79.PubMedCrossRefGoogle Scholar
  90. 90.
    Maeda K, Chung YS, Ogawa Y, Takatsuka S, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996;77:858–63.PubMedCrossRefGoogle Scholar
  91. 91.
    Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, et al. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56:2671–6.PubMedGoogle Scholar
  92. 92.
    Cortes-Funes H. The role of antiangiogenesis therapy: bevacizumab and beyond. Clin Transl Oncol. 2009;11:349–55.PubMedCrossRefGoogle Scholar
  93. 93.
    Shah MA, Ramanathan RK, Ilson DH, Levnor A, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006;24:5201–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29:868–74.PubMedCrossRefGoogle Scholar
  95. 95.
    Enzinger P, Ryan D, Regan E, Lehman N et al (2008) Phase II trial of docetaxel, cisplatin, irinotecan, and bevacizumab in metastatic esophagogastric cancer. J Clin Oncol 26:4552Abstr.Google Scholar
  96. 96.
    El-Rayes BF, Zalupski M, Bekai-Saab T, Heilbrun LK, et al. A phase II study of bevacizumab, oxaliplatin, and docetaxel in locally advanced and metastatic gastric and gastroesophageal junction cancers. Ann Oncol. 2010;21:1999–2004.PubMedCrossRefGoogle Scholar
  97. 97.
    Ohtsu A, Shah MA, Van Cutsem E, Rha SY, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.PubMedCrossRefGoogle Scholar
  98. 98.
    Shah M, Van Cutsem E, Kang Y, Dakhil SR et al (2012) Survival analysis according to disease subtype in AVAGAST: First-line capecitabine and cisplatin plus bevacizumab (bev) or placebo in patients (pts) with advanced gastric cancer. J Clin Oncol (Meeting Abstracts) 30:4(suppl 5).Google Scholar
  99. 99.
    Van Cutsem E, Yeh KH, Bang YJ, Shen L et al (2012) Phase III trial of everolimus (EVE) in previously treated patients with advanced gastric cancer (AGC): GRANITE-1. J Clin Oncol 30(suppl 4):LBA3.Google Scholar
  100. 100.
    Cappetta A, Lonardi S, Pastorelli D, Bergamo F, et al. Advanced gastric cancer (GC) and cancer of the gastro-oesophageal junction (GEJ): focus on targeted therapies. Crit Rev Oncol Hematol. 2012;81:38–48.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1. Faculty of Medicine, Department of Medical OncologyUludag UniversityBursaTurkey
  2. 2.Gastrointestinal Oncology Program, Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations