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Gastric Cancer: Chemotherapy for Advanced Disease with Special Focus on Studies from Japan

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Abstract

Unresectable or metastatic advanced gastric cancer (AGC) is non-curable, and median survival time (MST) is about 3 months when best supportive care (BSC) is performed. By chemotherapy, MST has been extended to about 13–14 months, and symptomatic relief can be expected by high tumor shrinkage effect (Murad et al., Cancer 72:37–41, 1993).

In the primary treatment, the standard treatment was decided internationally as a combination therapy of pushed pyrimidine and platinum, and treatment strategy was individualized by expression of HER2 protein. In second-line treatment, weekly paclitaxel (PTX) + ramucirumab (RAM) therapy is considered as standard. For third-line therapy, the survival prolonging effect of immune checkpoint inhibitors, which is attracting attention in many types of cancer in recent years, was also observed in gastric cancer. Nivolumab has shown significant survival extension effect in salvage line study. Thus, in recent years, standardization of treatment strategies and individualization based on biomarkers have been in progress, and further approval of new agents is expected to extend overall survival. On the other hand, treatment for the elderly and patients with severe peritoneal metastasis, which are not eligible to receive standard treatment, has not been established and is a future clinical problem. In this chapter, we discuss about treatment strategies and prospects for unresectable/recurrent gastric cancer.

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References

  1. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72:37–41.

    Article  CAS  Google Scholar 

  2. Glimelius B, Hoffman K, Haglund U, Nyrén O, Sjödén PO, et al. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol. 1994;5:189–90.

    Article  CAS  Google Scholar 

  3. Cullinan SA, Moertel CG, Wieand HS, O’Connell MJ, Poon MA, et al. Controlled evaluation of three drug combination regimens versus fluoroouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group. J Clin Oncol. l994;12:412–8.

    Article  CAS  Google Scholar 

  4. Kim NK, Park YS, Heo DS, Suh C, Kim SY, et al. A phase lll 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;71:3813–8.

    Article  CAS  Google Scholar 

  5. Ohtsu A, ShimadaY SK, Boku N, Hyodo I, et al. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus Mitomycin C in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study JCOG9205. J Clin Oncol. 2003;21:54–9.

    Article  CAS  Google Scholar 

  6. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, et al. F1uoroulacil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomized phase3 study. Lancet Oncol. 2009;10:1063.

    Article  CAS  Google Scholar 

  7. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, 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.

    Article  CAS  Google Scholar 

  8. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. 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;20:666–73.

    Article  Google Scholar 

  9. Yamaguchi K, Sawaki A, Doi T, Satoh T, Yamada Y, Omuro Y, et al. Efficacy and safety of capecitabine plus cisplatin in Japanese patients with advanced or metastatic gastric cancer: subset analyses of the AVAGAST study and the ToGA study. Gastric Cancer. 2013;16:175–82.

    Article  CAS  Google Scholar 

  10. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, 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.

    Article  Google Scholar 

  13. Koizumi W, Kim YH, Fujii M, Imamura H, Lee KH, et al. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014;140:319–28.

    Article  CAS  Google Scholar 

  14. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015;26:141–8.

    Article  CAS  Google Scholar 

  15. Thuss-Patience PC, Kretzschmar A, Dogan Y, Rothmann F, Blau I, et al. 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;47:2306–14.

    Article  CAS  Google Scholar 

  16. Kang JH, Lee SI, Lim DH, Park KW, Oh SY, et al. 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;30:1513–8.

    Article  CAS  Google Scholar 

  17. Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15:78–86.

    Article  CAS  Google Scholar 

  18. Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, et al. 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;31:4438–44.

    Article  CAS  Google Scholar 

  19. Cunningham D, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017;18(3):357–70.

    Article  CAS  Google Scholar 

  20. Hecht JR, Bang YJ, Qin SK, Chung HC, Xu J, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC—a randomized phase III trial. J Clin Oncol. 2016;34:443–5.

    Article  CAS  Google Scholar 

  21. Shen L. 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. 2015;18(1):168–76.

    Article  CAS  Google Scholar 

  22. Waddell T. 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.

    Article  CAS  Google Scholar 

  23. Lordic F. 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.

    Article  Google Scholar 

  24. Catenacci DVT, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(11):1467–82.

    Article  CAS  Google Scholar 

  25. Shah MA, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 2017;3(5):620–7.

    Article  Google Scholar 

  26. Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu J, et al. 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.

    Article  CAS  Google Scholar 

  27. Ohtus A, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31(31):3935–43.

    Article  Google Scholar 

  28. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.

    Article  CAS  Google Scholar 

  29. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, 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.

    Article  CAS  Google Scholar 

  30. Bang YJ, et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1637–51.

    Article  CAS  Google Scholar 

  31. Matsusaka S, Nashimoto A, Nishikawa K, Miki A, Miwa H, et al. Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101). Gastric Cancer. 2016;19:839–51.

    Article  CAS  Google Scholar 

  32. Sawaki A, Ohashi Y, Omuro Y, Satoh T, Hamamoto Y, et al. Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study. Gastric Cancer. 2012;15:313–22.

    Article  CAS  Google Scholar 

  33. Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18:640–53.

    Article  CAS  Google Scholar 

  34. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71.

    Article  CAS  Google Scholar 

  35. Hironaka S, Sugimoto N, Yamaguchi K, et al. S-1 plus leucovorin versus S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer: a randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(1):99–108.

    Article  CAS  Google Scholar 

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Correspondence to Taroh Satoh .

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Satoh, T. (2019). Gastric Cancer: Chemotherapy for Advanced Disease with Special Focus on Studies from Japan. In: Shiotani, A. (eds) Gastric Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-13-1120-8_12

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  • DOI: https://doi.org/10.1007/978-981-13-1120-8_12

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