Skip to main content
SpringerLink
Log in

Systemic Treatment for Metastatic or Recurrent Disease

  • Chapter
Esophageal Cancer

Abstract

The majority of patients with esophageal cancer develop metastasis during the course of their disease. Chemotherapy, therefore, remains the mainstay of treatment of patients with advanced esophageal cancer and is predominantly used to prolong survival and preserve quality of life. According to data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, the 5-year survival for patients with esophageal cancer improved only modestly over the last 50 years, from 4 % in the years 1950–1954 to 12–17 % during the period 1994–2002 and 20 % in 2006. Despite a large number of clinical trials, there is no consensus as to the best regimen for initial treatment of patients with advanced gastroesophageal cancer. In the majority of cases, chemotherapy for advanced esophageal and esophagogastric junction (GEJ) adenocarcinoma, squamous cell carcinoma of the esophagus, and gastric adenocarcinoma is often used interchangeably.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;(3):CD004064. doi:10.1002/14651858.CD004064.pub3.

  2. Statistics SC. 2011. http://seer.cancer.gov/statfacts/html/stomach.html. Accessed 25 July 2014.

  3. Ajani JA, Barthel JS, Bekaii-Saab T, Bentrem DJ, D’Amico TA, Fuchs CS, Gerdes H, Hayman JA, Hazard L, Ilson DH, Kleinberg LR, McAleer MF, Meropol NJ, Mulcahy MF, Orringer MB, Osarogiagbon RU, Posey JA, Sasson AR, Scott WJ, Shibata S, Strong VE, Swisher SG, Washington MK, Willett C, Wood DE, Wright CD, Yang G. Esophageal cancer. J Natl Compr Canc Netw. 2008;6(9):818–49.

    PubMed  Google Scholar 

  4. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24(18):2903–9. doi:10.1200/jco.2005.05.0245.

    Article  CAS  PubMed  Google Scholar 

  5. Ilson DH. Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol. 2007;25(22):3188–90. doi:10.1200/jco.2006.10.2210.

    Article  CAS  PubMed  Google Scholar 

  6. Bleiberg H, Conroy T, Paillot B, Lacave AJ, Blijham G, Jacob JH, Bedenne L, Namer M, De Besi P, Gay F, Collette L, Sahmoud T. Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer. 1997;33(8):1216–20.

    Article  CAS  PubMed  Google Scholar 

  7. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA, Group VS. 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(31):4991. doi:10.1200/jco.2006.06.8429.

    Article  PubMed  Google Scholar 

  8. Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29(7):868–74. doi:10.1200/jco.2010.32.0770.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Van Cutsem E, Boni C, Tabernero J, Massuti B, Richards D, Prenen H, Steinberg I, Rougier P. Randomized phase II study (GATE study) of docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer. In: ASCO Annual Meeting, Chicago; 2011.

    Google Scholar 

  10. Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jager E. 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. Ann Oncol. 2008;19(11):1882–7. doi:10.1093/annonc/mdn403.

    Article  PubMed  Google Scholar 

  11. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46. doi:10.1056/NEJMoa073149.

    Article  CAS  PubMed  Google Scholar 

  12. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jager E. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26(9):1435–42. doi:10.1200/jco.2007.13.9378.

    Article  CAS  PubMed  Google Scholar 

  13. Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. 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(8):1450–7. doi:10.1093/annonc/mdn166.

    Article  CAS  PubMed  Google Scholar 

  14. Pozzo C, Barone C, Szanto J, Padi E, Peschel C, Bukki J, Gorbunova V, Valvere V, Zaluski J, Biakhov M, Zuber E, Jacques C, Bugat R. Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol. 2004;15(12):1773–81. doi:10.1093/annonc/mdh473.

    Article  CAS  PubMed  Google Scholar 

  15. Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. 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(9):1547–53. doi:10.1200/jco.2009.25.4706.

    Article  CAS  PubMed  Google Scholar 

  16. Kornek GV, Raderer M, Schull B, Fiebiger W, Gedlicka C, Lenauer A, Depisch D, Schneeweiss B, Lang F, Scheithauer W. Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer. Br J Cancer. 2002;86(12):1858–63. doi:10.1038/sj.bjc.6600345.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Roth AD, Maibach R, Martinelli G, Fazio N, Aapro MS, Pagani O, Morant R, Borner MM, Herrmann R, Honegger H, Cavalli F, Alberto P, Castiglione M, Goldhirsch A. 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(3):301–6.

    Article  CAS  PubMed  Google Scholar 

  18. Roy A, Cunningham D, Hawkins R, Sorbye H, Adenis A, Barcelo JR, Lopez-Vivanco G, Adler G, Canon JL, Lofts F, Castanon C, Fonseca E, Rixe O, Aparicio J, Cassinello J, Nicolson M, Mousseau M, Schalhorn A, D’Hondt L, Kerger J, Hossfeld DK, Garcia Giron C, Rodriguez R, Schoffski P, Misset JL. Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study. Br J Cancer. 2012;107(3):435–41. doi:10.1038/bjc.2012.286.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Park SH, Lee WK, Chung M, Lee Y, Han SH, Bang SM, Cho EK, Shin DB, Lee JH. Paclitaxel versus docetaxel for advanced gastric cancer: a randomized phase II trial in combination with infusional 5-fluorouracil. Anticancer Drugs. 2006;17(2):225.

    Article  CAS  PubMed  Google Scholar 

  20. Bouche O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsene D, Paitel JF, Guerin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study–FFCD 980. J Clin Oncol. 2004;22(21):4319–28. doi:10.1200/jco.2004.01.140.

    Article  CAS  PubMed  Google Scholar 

  21. Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. 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(1):72–80. doi:10.1007/s10120-011-0009-5.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, Kang YK, Shin DB, Kim HT, Kim HJ, et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer. 1993;71(12):3813–8.

    Article  CAS  PubMed  Google Scholar 

  23. Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994;5(7):609–16.

    CAS  PubMed  Google Scholar 

  24. Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997;15(1):261.

    Article  CAS  PubMed  Google Scholar 

  25. Yun J, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A randomised phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced gastric cancer. Eur J Cancer. 2010;46(5):885–91. doi:10.1016/j.ejca.2009.12.015.

    Article  CAS  PubMed  Google Scholar 

  26. Preusser P, Wilke H, Achterrath W, Fink U, Lenaz L, Heinicke A, Meyer J, Meyer HJ, Buente H. Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer. J Clin Oncol. 1989;7(9):1310–7.

    CAS  PubMed  Google Scholar 

  27. Kelsen D, Atiq OT, Saltz L, Niedzwiecki D, Ginn D, Chapman D, Heelan R, Lightdale C, Vinciguerra V, Brennan M. FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer. J Clin Oncol. 1992;10(4):541–8.

    CAS  PubMed  Google Scholar 

  28. Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol. 2000;18(14):2648–57.

    CAS  PubMed  Google Scholar 

  29. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20(4):666–73. doi:10.1093/annonc/mdn717.

    Article  PubMed  Google Scholar 

  30. Lord SR, Hall PS, Seymour MT. Are we representing the true population in oncology trials? Ann Oncol. 2009;20(12):2022. doi:10.1093/annonc/mdp461.

    Article  CAS  PubMed  Google Scholar 

  31. Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D. Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol. 2009;20(9):1529–34. doi:10.1093/annonc/mdp047.

    Article  CAS  PubMed  Google Scholar 

  32. Fornaro L, Vasile E, Masi G, Loupakis F, Caponi S, Ginocchi L, Falcone A. Capecitabine after gastrectomy for advanced gastric cancer: have we got the patient right? Ann Oncol. 2010;21(1):181. doi:10.1093/annonc/mdp469.

    Article  CAS  PubMed  Google Scholar 

  33. Chen S, Feng X, Li Y, Yuan X, Zhou Z, Chen Y. Efficacy and safety of XELOX and FOLFOX6 adjuvant chemotherapy following radical total gastrectomy. Oncol Lett. 2012;3(4):781–6. doi:10.3892/ol.2012.577.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzen F, Noh SH. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315–21. doi:10.1016/s0140-6736(11)61873-4.

    Article  CAS  PubMed  Google Scholar 

  35. Yoney A, Isikli L. Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Asian Pac J Cancer Prev. 2013;14(9):5127–31.

    Article  PubMed  Google Scholar 

  36. Petrasch S, Welt A, Reinacher A, Graeven U, Konig M, Schmiegel W. Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer. 1998;78(4):511–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Polee MB, Eskens FA, van der Burg ME, Splinter TA, Siersema PD, Tilanus HW, Verweij J, Stoter G, van der Gaast A. Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer. Br J Cancer. 2002;86(5):669–73. doi:10.1038/sj.bjc.6600166.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Ilson DH, Forastiere A, Arquette M, Costa F, Heelan R, Huang Y, Kelsen DP. A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus. Cancer J. 2000;6(5):316–23.

    CAS  PubMed  Google Scholar 

  39. Zhang X, Shen L, Li J, Li Y, Li J, Jin M. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol. 2008;31(1):29–33. doi:10.1097/COC.0b013e3181131ca9.

    Article  PubMed  Google Scholar 

  40. Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003;26(1):37–41.

    Article  CAS  PubMed  Google Scholar 

  41. Park KW, Ahn JS, Park YS, Lee J, Kang JH, Park JO, Lim HY, Im YH, Kang WK, Park K, Lee SI. Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer. Cancer Chemother Pharmacol. 2007;59(1):17–21. doi:10.1007/s00280-006-0253-2.

    Article  CAS  PubMed  Google Scholar 

  42. Kim KH, Jeung KJ, Kim HJ, Bae SB, Kim CK, Lee NS, Lee KT, Park SK, Won JH, Hong DS, Park HS. Phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with recurrent or metastatic gastric cancer. Cancer Res Treat. 2007;39(2):49–53. doi:10.4143/crt.2007.39.2.49.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Fahlke J, Ridwelski K, Schmidt C, Hribaschek K, Stuebs P, Kettner E, Quietzsch D, Assmann M, Deist T, Keilholz U, Lippert H. A multicentre phase II study of docetaxel plus cisplatin for the treatment of advanced gastric cancer. Chemotherapy. 2007;53(6):454–60. doi:10.1159/000110042.

    Article  CAS  PubMed  Google Scholar 

  44. Di Bartolomeo M, Buzzoni R, Mariani L, Ferrario E, Katia D, Gevorgyan A, Zilembo N, Bordonaro R, Bochicchio AM, Massidda B, Ardizzoia A, Marini G, Aitini E, Schieppati G, Comella G, Pinotti G, Palazzo S, Cicero G, Bajetta E, Villa E, Fagnani D, Reguzzoni G, Agostana B, Oliani C, Kildani B, Duro M, Botta M, Mozzana R, Mantovani G. Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial. Oncology. 2006;71(5–6):341–6. doi:10.1159/000108575.

    Article  PubMed  Google Scholar 

  45. Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010;21(1):71–7. doi:10.1093/annonc/mdp269.

    Article  CAS  PubMed  Google Scholar 

  46. Luo HY, Wang ZQ, Wang FH, Qiu MZ, Teng KY, Ruan DY, He YJ, Li YH, Xu RH. Phase 2 study of capecitabine and irinotecan combination chemotherapy (modified XELIRI regimen) in patients with advanced gastric cancer. Am J Clin Oncol. 2011;34(6):555–60. doi:10.1097/COC.0b013e3181f47ac1.

    Article  CAS  PubMed  Google Scholar 

  47. Oh SC, Sur HY, Sung HJ, Choi IK, Park SS, Seo JH, Jeen YT, Chun HJ, Shin SW, Mok YJ, Kim JS, Kim YH. A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer. Br J Cancer. 2007;96(10):1514–9. doi:10.1038/sj.bjc.6603752.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. MacDonald JS, Schein PS, Woolley PV, Smythe T, Ueno W, Hoth D, Smith F, Boiron M, Gisselbrecht C, Brunet R, Lagarde C. 5-Fluorouracil, doxorubicin, and mitomycin (FAM) combination chemotherapy for advanced gastric cancer. Ann Intern Med. 1980;93(4):533–6.

    Article  CAS  PubMed  Google Scholar 

  49. Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, et al. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985;253(14):2061–7.

    Article  CAS  PubMed  Google Scholar 

  50. A randomized, comparative study of combination chemotherapies in advanced gastric cancer: 5-fluorouracil and cisplatin (FP) versus 5-fluorouracil, cisplatin, and 4’-epirubicin (FPEPIR). Kyoto Research Group for Chemotherapy of Gastric Cancer (KRGCGC). Anticancer Res. 1992;12(6b):1983–8.

    Google Scholar 

  51. Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. 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 Clin Oncol. 2002;20(8):1996–2004.

    Article  CAS  PubMed  Google Scholar 

  52. Lerner A, Gonin R, Steele Jr GD, Mayer RJ. Etoposide, doxorubicin, and cisplatin chemotherapy for advanced gastric adenocarcinoma: results of a phase II trial. J Clin Oncol. 1992;10(4):536–40.

    CAS  PubMed  Google Scholar 

  53. Wilke H, Preusser P, Fink U, Achterrath W, Lenaz L, Stahl M, Schober C, Link H, Meyer HJ, Lucke B, et al. High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer–a phase II study in elderly patients or patients with cardiac risk. Invest New Drugs. 1990;8(1):65–70.

    Article  CAS  PubMed  Google Scholar 

  54. di Bartolomeo M, Bajetta E, de Braud F, Bochicchio AM, Gebbia V, Bozzetti F, Doci R, Bonfanti G, Cozzaglio L. Phase II study of the etoposide, leucovorin and fluorouracil combination for patients with advanced gastric cancer unsuitable for aggressive chemotherapy. Oncology. 1995;52(1):41–4.

    Article  PubMed  Google Scholar 

  55. Catalano V, Graziano F, Santini D, D’Emidio S, Baldelli AM, Rossi D, Vincenzi B, Giordani P, Alessandroni P, Testa E, Tonini G, Catalano G. Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer. 2008;99(9):1402–7. doi:10.1038/sj.bjc.6604732.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15(1):78–86. doi:10.1016/s1470-2045(13)70549-7.

    Article  CAS  PubMed  Google Scholar 

  57. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012;30(13):1513–8. doi:10.1200/jco.2011.39.4585.

    Article  CAS  PubMed  Google Scholar 

  58. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.

    Google Scholar 

  59. Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013;24(6):1567–73. doi:10.1093/annonc/mdt002.

    Article  CAS  PubMed  Google Scholar 

  60. Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. 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 Clin Oncol. 2013;31(35):4438–44. doi:10.1200/jco.2012.48.5805.

    Article  CAS  PubMed  Google Scholar 

  61. Wilke HV, Custem Van E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim T-Y, Cunningham D, Rougier P, Emig M, Carlesi R, Chandrawansa K, Muro K, Ohtsu A. RAINBOW: a global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. Paper presented at the ASCO Annual Meeting 2014, Chicago, 2014.

    Google Scholar 

  62. Tanaka T, Fujita H, Sueyoshi S, Tanaka Y, Sasahara H, Mori N, Nagano T, Yamana H, Shirouzu K. Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. Chemotherapy. 2007;53(6):449–53. doi:10.1159/000110018.

    Article  CAS  PubMed  Google Scholar 

  63. Lorenzen S, Duyster J, Lersch C, von Delius S, Hennig M, Bredenkamp R, Peschel C, Lordick F. Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial. Br J Cancer. 2005;92(12):2129–33. doi:10.1038/sj.bjc.6602645.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Osaka Y, Takagi Y, Hoshino S, Tachibana S, Tsuchida A, Aoki T. Combination chemotherapy with docetaxel and nedaplatin for recurrent esophageal cancer in an outpatient setting. Dis Esophagus. 2006;19(6):473–6. doi:10.1111/j.1442-2050.2006.00614.x.

    Article  CAS  PubMed  Google Scholar 

  65. Burkart C, Bokemeyer C, Klump B, Pereira P, Teichmann R, Hartmann JT. A phase II trial of weekly irinotecan in cisplatin-refractory esophageal cancer. Anticancer Res. 2007;27(4c):2845–8.

    CAS  PubMed  Google Scholar 

  66. Minamide J, Aoyama N, Takada K, Oota Y. Evaluation of docetaxel, CDDP and 5-FU combined therapy as second-line chemotherapy for esophagus cancer. Gan To Kagaku Ryoho. 2007;34(1):49–52.

    PubMed  Google Scholar 

  67. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. 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). Eur J Cancer. 2011;47(15):2306–14. doi:10.1016/j.ejca.2011.06.002.

    Article  CAS  PubMed  Google Scholar 

  68. Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014;50(8):1437–45. doi:10.1016/j.ejca.2014.01.020.

    Article  CAS  PubMed  Google Scholar 

  69. Sym SJ, Hong J, Park J, Cho EK, Lee JH, Park YH, Lee WK, Chung M, Kim HS, Park SH, Shin DB. A randomized phase II study of biweekly irinotecan monotherapy or a combination of irinotecan plus 5-fluorouracil/leucovorin (mFOLFIRI) in patients with metastatic gastric adenocarcinoma refractory to or progressive after first-line chemotherapy. Cancer Chemother Pharmacol. 2013;71(2):481–8. doi:10.1007/s00280-012-2027-3.

    Article  CAS  PubMed  Google Scholar 

  70. Hu Y, Bandla S, Godfrey TE, Tan D, Luketich JD, Pennathur A, Qiu X, Hicks DG, Peters JH, Zhou Z. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma. Mod Pathol. 2011;24(7):899–907. doi:10.1038/modpathol.2011.47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Hecht JR, Bang YJ, QQin S. Lapatinib in combination with capecitabine plus oxaliplatin (CAPOX) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: the TRIO-013/LOGiC trial In: ASCO Annual Meeting, 2013.

    Google Scholar 

  72. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK. 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. doi:10.1016/s0140-6736(10)61121-x.

    Article  CAS  PubMed  Google Scholar 

  73. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. 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(30):3968–76. doi:10.1200/jco.2011.36.2236.

    Article  CAS  PubMed  Google Scholar 

  74. Shen L, Li J, Xu J, Pan H, Dai G, Qin S, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2015;18(1):168–76.

    Google Scholar 

  75. Yoon H, Bendell J, Braiteh F, Firdaus I, Philip P, Cohn A, Lewis N, Anderson D, Arrowsmith E, Schwartz H, Xu Y, Koshiji M, Alberts S, Wainberg Z. Ramucirumab (RAM) plus FOLFOX as front-line therapy (Rx) for advanced gastric or esophageal adenocarcinoma (GE-AC): randomized, double-blind, multicenter phase 2 trial. In: ASCO Annual Meeting, Vol. 5s. Chicago; 2014.

    Google Scholar 

  76. Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):481–9. doi:10.1016/s1470-2045(13)70096-2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Gotte H, Melezinkova H, Moehler M. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):490–9. doi:10.1016/s1470-2045(13)70102-5.

    Article  CAS  PubMed  Google Scholar 

  78. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res. 1993;53(19):4727.

    CAS  PubMed  Google Scholar 

  79. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58. doi:307/5706/58 [pii].

    Article  CAS  PubMed  Google Scholar 

  80. Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, Peng Yong W, Langer B, Delmar P, Scherer SJ, Shah MA. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30(17):2119. doi:10.1200/jco.2011.39.9824; 10.1200/jco.2011.39.9824.

  81. Ebos JM, Lee CR, Bogdanovic E, Alami J, Van Slyke P, Francia G, Xu P, Mutsaers AJ, Dumont DJ, Kerbel RS. Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth. Cancer Res. 2008;68(2):521. doi:10.1158/0008-5472.can-07-3217; 10.1158/0008-5472.can-07-3217.

  82. Lambrechts D, Claes B, Delmar P, Reumers J, Mazzone M, Yesilyurt BT, Devlieger R, Verslype C, Tejpar S, Wildiers H, de Haas S, Carmeliet P, Scherer SJ, Van Cutsem E. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol. 2012;13(7):724. doi:10.1016/s1470-2045(12)70231-0; 10.1016/s1470-2045(12)70231-0.

  83. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998;92(6):735. doi:S0092-8674(00)81402-6 [pii].

    Article  CAS  PubMed  Google Scholar 

  84. Yamashita-Kashima Y, Fujimoto-Ouchi K, Yorozu K, Kurasawa M, Yanagisawa M, Yasuno H, Mori K. Biomarkers for antitumor activity of bevacizumab in gastric cancer models. BMC Cancer. 2012;12:37. doi:10.1186/1471-2407-12-37; 10.1186/1471-2407-12-37.

  85. Kim MA, Lee HS, Lee HE, Jeon YK, Yang HK, Kim WH. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number. Histopathology. 2008;52(6):738–46. doi:10.1111/j.1365-2559.2008.03021.x.

    Article  CAS  PubMed  Google Scholar 

  86. Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Cote JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992. doi:10.1158/0008-5472.can-06-0191.

    Article  CAS  PubMed  Google Scholar 

  87. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. 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 Clin Oncol. 2014;32(19):2039–49. doi:10.1200/jco.2013.53.6136.

    Article  CAS  PubMed  Google Scholar 

  88. Dutton SJ, Ferry DR, Blazeby JM, Abbas H, Dahle-Smith A, Mansoor W, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. The Lancet Oncology. 2014;15(8):894–904.

    Google Scholar 

  89. Kang YK, Muro K, Ryu MH, Yasui H, Nishina T, Ryoo BY, Kamiya Y, Akinaga S, Boku N. A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs. 2014;32(2):355–61. doi:10.1007/s10637-013-0057-2.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research institute, 320 W 10th Avenue, Columbus, OH, 43210, USA

    Sameh Mikhail MD

  2. Gastrointestinal Oncology, The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research institute, 320 W 10th Avenue, Columbus, OH, 43210, USA

    Tanios Bekaii-Saab MD

Authors
  1. Sameh Mikhail MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tanios Bekaii-Saab MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sameh Mikhail MD .

Editor information

Editors and Affiliations

  1. Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USA

    Nabil F. Saba

  2. Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USA

    Bassel F. El-Rayes

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Mikhail, S., Bekaii-Saab, T. (2015). Systemic Treatment for Metastatic or Recurrent Disease. In: Saba, N., El-Rayes, B. (eds) Esophageal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-20068-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-20068-2_14

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-20067-5

  • Online ISBN: 978-3-319-20068-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation