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01-12-2017 | Upper Gastrointestinal Cancers (L Rajdev, Section Editor)

The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer

Authors: Elizabeth Cartwright, MBBS, David Cunningham, MD FRCP

Published in: Current Treatment Options in Oncology | Issue 12/2017

Opinion statement

Approximately 20% of patients with cancer of the stomach or gastro-oesophageal junction (GOJ) present with resectable disease. Long-term outcome after surgery alone in these patients is poor, and a combined treatment approach is the standard of care. The two approaches to managing patients with cancer of the GOJ are perioperative chemotherapy or preoperative chemoradiotherapy. Based upon the most recent evidence, patients treated with a perioperative approach and deemed suitable for a triplet regimen should be considered for pre- and post-operative FLOT (5-fluorouracil [5-FU], leucovorin, oxaliplatin and docetaxel) and those suitable for a doublet regimen should be considered for a fluoropyrimidine/platinum combination such as capecitabine and oxaliplatin. Alternatively, such patients may be considered for preoperative chemoradiotherapy according to the CROSS regimen. True gastric cancers may be treated with a perioperative approach or, as is commonly used in Asia, postoperative adjuvant chemotherapy.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patters in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. https://doi.org/10.1002/ijc.29210.CrossRefPubMed

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. https://doi.org/10.3322/caac.21262.CrossRefPubMed

• Smyth EC, Lagergren J, Fitzgerald RC, Lordick F, Shah MA, Lagergren P, et al. Oesophageal cancer. Nat Rev Dis Primers. 2017;3:10748. https://doi.org/10.1038/nrdp.2017.48.A comprehensive review of oesophageal cancerCrossRef

Rusch VW. Are cancers of the esophagus, gastroesophageal junction, and cardia one disease, two, or several? Semin Oncol. 2004;31(4):444–9. https://doi.org/10.1053/j.seminoncol.2004.04.023.CrossRefPubMed

Baus MF, Vaughan TL. Epidemiology and risk factors for gastroesophageal tumors: understanding the rising incidence of this disease. Semin Radiat Oncol. 2013;23(1):3–9. https://doi.org/10.1016/j.semradonc.2012.09.008.CrossRef

Rustgi AK, El-Serag HB. Esophageal carcinoma. N Engl J Med. 2014;371(26):2499–509. https://doi.org/10.1056/NEJMra1314530.CrossRefPubMed

Anderson LA, Watson PRG, Murphy SJ, Johnston BT, Comber H, Guigan JM, et al. Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma: results from the FINBAR study. World J Gastroenterol. 2007;13(10):1585–94. https://doi.org/10.3748/wjg.v13.i10.1585.CrossRefPubMedPubMedCentral

Cook MB, Corley DA, Murray LJ, Liao LM, Kamangar F, Ye W, et al. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett’s and esophageal adenocarcinoma consortium (BEACON). PLoS One. 2014;9(7):e103508. https://doi.org/10.1371/journal.pone.0103508.CrossRefPubMedPubMedCentral

Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European cancer observatory. Eur J Cancer. 2015;51(9):1164–87. https://doi.org/10.1016/j.ejca.2013.09.002.CrossRefPubMed

10.

Zhao J, He YT, Zheng RS, Zhang SW, Chen WQ. Analysis of esophageal cancer time trends in China, 1989–2008. Asian Pac J Cancer Prev. 2012;13(9):4613–7. https://doi.org/10.7314/APJCP.2012.13.9.4613.CrossRefPubMed

11.

Prabhu A, Obi KO, Rubenstein JH. The synergistic effects of alcohol and tobacco consumption on the risk of esophageal squamous cell carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109(6):822–7. https://doi.org/10.1038/ajg.2014.71.CrossRefPubMed

12.

Rice TW, Rusch VW, Ishwaran H, Blackstone EH. Cancer of the esophagus and esophagogastric junction data-driven staging for the seventh edition of the American joint committee on cancer/International Union against cancer cancer staging manuals. Cancer. 2010;11616:3763–73. https://doi.org/10.1002/cncr.25146.CrossRef

13.

• Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v38–49. https://doi.org/10.1093/annonc/mdw350.European clinical practice guidelinesCrossRefPubMed

14.

• Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v50–7. https://doi.org/10.1093/annonc/mdw329.European clinical practice guidelinesCrossRefPubMed

15.

Dykewicz CA. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Clin Infect Dis. 2001;33(2):139–44. https://doi.org/10.1086/321805.CrossRefPubMed

16.

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. https://doi.org/10.1056/NEJMoa055531.CrossRefPubMed

17.

Davies AR, Gossage JA, Zylstra J, Mattsson F, Lagergren J, Maisey N, et al. Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol. 2014;32(27):3983–90. https://doi.org/10.1200/JCO.2014.55.9070.CrossRef

18.

•• Al-Batran SE, Homann N, Schmalenberg H, Kopp HG, Haag GM, Luley KB, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicentre, randomized phase 3 trial. J Clin Oncol. 2017;35(suppl 15):4004. https://doi.org/10.1200/JCO.2017.35.15_suppl.4004.A study that reports on a new standard of care in perioperative chemotherapy

19.

Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicentre phase III trial. J Clin Oncol. 2011;29913:1715–21. https://doi.org/10.1200/JCO.2010.33.0597.CrossRef

20.

Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7. https://doi.org/10.1200/JCO.2009.22.2083.CrossRefPubMed

21.

•• Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–8. https://doi.org/10.1016/SI470-2045(15)00040-6.Long-term follow-up results of a study that defined preoperative chemoradiotherapy as a standard of care in oesophageal and junctional cancerCrossRefPubMed

22.

Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30. https://doi.org/10.1056/NEJMoa010187.CrossRefPubMed

23.

Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387–93. https://doi.org/10.1200/JCO.2011.36.5908.CrossRefPubMed

24.

•• Bang Y-J, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet Oncol. 2012;379(9813):315–21. https://doi.org/10.1016/S0140-6736(11)61873-4.A study that reports survival benefit of adjuvant chemotherapy in resected gastric cancerCrossRef

25.

Al-Batran S-E, Hofheinz RD, Pauligk C, Kopp H-G, Haag GM, Luley KB, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin, versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4:AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016;17(12):1697–708. https://doi.org/10.1016/S1470-2045(16)30531-9.CrossRefPubMed

26.

Medical Research Council Oesophageal Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359(9319):1727–33. https://doi.org/10.1016/S0140-6736(02)08651-8.CrossRef

27.

Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, et al. Long-term results of RTOG trial 8911 (USA intergroup 113): a randomised assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25(24):3719–25. https://doi.org/10.1200/JCO.2006.10.4760.CrossRefPubMed

28.

Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European organisation for research and treatment of cancer randomized trial 40954. J Clin Oncol. 2010;28(35):5210–8. https://doi.org/10.1200/JCO.2009.26.6114.CrossRefPubMedPubMedCentral

29.

Gebski V, Burmeister B, Smithers MB, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8(3):226–34. https://doi.org/10.1016/S1470-2045(07)70039-6.CrossRefPubMed

30.

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92. https://doi.org/10.1016/S1470-2045(11)70142-5.CrossRefPubMed

31.

Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49(15):3149–58. https://doi.org/10.1016/j.ejca.2013.05.029.CrossRefPubMed

32.

Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017;S1470-2045(17):30447–3. https://doi.org/10.1016/S1470-2045(17)30447-3.

33.

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. https://doi.org/10.1056/NEJMoa1112088.CrossRefPubMed

34.

Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23(10):2310–7. https://doi.org/10.1200/JCO.2005.00.034.CrossRefPubMed

35.

Bedenne L, Michel P, Bouche O, Milan C, Mariette C, Conroy T, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cell cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007;25(10):1160–8. https://doi.org/10.1200/JCO.2005.04.7118.CrossRefPubMed

36.

Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327–33. https://doi.org/10.1200/JCO.2011.36.7136.CrossRefPubMedPubMedCentral

37.

Dikken JL, Jansen EP, Cats A, Bakker B, Hartgrink HH, Kranenbarg EMK, et al. Impact of the extent of surgery and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin Oncol. 2010;28(14):2430–6. https://doi.org/10.1200/JCO.2009.26.9654.CrossRefPubMed

38.

Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completed resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30(3):268–73. https://doi.org/10.1200/JCO.2011.39.1953.CrossRefPubMed

39.

Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, et al. Phase III trial to compare adjuvant chemotherapy with capeciatabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumours trial, including survival and subset analyses. J Clin Oncol. 2015;33(28):3130–6. https://doi.org/10.1200/JCO.2014.58.3930.CrossRefPubMed

40.

Verheij M, Jansen EPM, Cats A, van Grieken NCT, Aaronson NK, Boot H, et al. A multicentre randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: first results from the CRITICS study. J Clin Oncol. 2016;34(suppl 15):4000. https://doi.org/10.1200/JCO.2016.34.15_suppl.4000.

41.

Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, et al. Benefit of adjvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303(17):1729–37. https://doi.org/10.1001/jama.2010.534.CrossRefPubMed

42.

Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK medical Reseach council STO3): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017;18(3):357–70. https://doi.org/10.1016/S1470-2045(17)30043-8.CrossRefPubMedPubMedCentral

43.

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-oesophgeal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefPubMed

44.

Rivera F, Jimenez P, Alfonso PG, Lopez C, Gallego J, Limon LM, et al. NeoHx study: perioperative treatment with trastuzumab in combination with capecitabine and oxaliplatin (XELOX-T) in patients with HER2 resectable stomach or esophagogastric junction (EJC) adenocarcinoma—R0 resection, pCR, and toxicity analysis. J Clin Oncol. 2013;31(suppl 15):4098. https://doi.org/10.1200/jco.2013.31.15_suppl.4098.

45.

Hofheinz R, Hegewisch-Becker S, Thuss-Patience PC, Kunzmann V, Fuchs M, Graeven U, et al. HER-FLOT: Trastuzumab in combination with FLOT as perioperative treatment for patients with HER2 positive locally advanced esophagogastric adenocarcinoma: a phase II trial of the AIO gastric cancer study group. J Clin Oncol. 2014;32(suppl 15):4073. https://doi.org/10.1200/jco.2014.32.15_suppl.4073.

Title: The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer
Authors: Elizabeth Cartwright, MBBS
David Cunningham, MD FRCP
Publication date: 01-12-2017
Publisher: Springer US
Published in: Current Treatment Options in Oncology / Issue 12/2017
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI: https://doi.org/10.1007/s11864-017-0510-0

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