Objetivo
Describir las características clínicas, los patrones de tratamiento y los costos asociados en pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina, en los sectores público y privado.

Métodos
Una cohorte histórica de pacientes que recibieron tratamiento de quimioterapia de primera línea (análogo de platino y/o una fluoropirimidina) y fueron seguidos durante al menos tres meses después de la última administración de un agente citotóxico de primera línea fueron elegibles. Se extrajeron los datos a través de un cuestionario estructurado a partir de los registros médicos de cuatro hospitales argentinos. Las estimaciones de los costos de tratamiento también se calcularon utilizando los costos unitarios de los hospitales participantes.

Resultados
Entre los 101 pacientes, más de tres cuartas partes (79,2%) eran hombres, 41,6% fueron diagnosticados con enfermedad metastásica en estadio IV, la edad media fue de 57,7 años y el 27,7% tenían antecedentes de tabaquismo. Antes del diagnóstico de cáncer gástrico metastásico, el 42,4% de los pacientes habían recibido gastrectomía total. El 97% de los pacientes recibió una terapia doble o triplete, de los cuales el tratamiento más frecuente fue la epirubicina en combinación con oxaliplatino y capecitabina (38%), seguida de capecitabina + oxaliplatino (29%). Alrededor del 36% de los pacientes respondieron al tratamiento de primera línea (respuesta completa y parcial). Del 76,2% de los pacientes que siguieron un tratamiento de segunda línea, al 37,7% todavía se les administró un análogo de platino y/o fluoropirimidina. Durante el período de seguimiento, el 50% de los pacientes progresó y el 32,8% tenía enfermedad estable. La terapia de apoyo consistió principalmente en visitas ambulatorias después de la última línea de quimioterapia (16,8%), radioterapia paliativa (16,8%) y cirugía (30,7%). Se observaron diferencias significativas entre los costos de los hospitales públicos y privado.

Conclusiones
Comprender los patrones de tratamiento en pacientes con cáncer gástrico localmente avanzado o metastásico puede ayudar a abordar las necesidades médicas no satisfechas para un mejor manejo del paciente y la mejora de sus resultados clínicos en Argentina.

Authors: Diego Novick[1], Guillermo Mendez[2], Marcela Carballido[3], Mariela Rizzo[3], Juan Manuel O'Connor[4], Javier Castillo[5], Daniel Lee Kay Pen[6], Sara Siddi [7], Demian Rodante[8], Maria Victoria Moneta[7], Josep Maria Haro[7]

Affiliation:
[1] Eli Lilly and Company, Windlesham, Surrey, UK
[2] Fundación Favaloro para la Docencia e Investigación Médica, Buenos Aires, Argentina
[3] Hospital de Gastroenterología “Dr. Carlos Bonorino Udaondo”, Buenos Aires, Argentina
[4] Instituto Alexander Fleming, Buenos Aires, Argentina
[5] Hospital Alemán Asociación Civil, Buenos Aires, Argentina
[6] LACAM Eli Lilly and Company, LIMA, Peru
[7] Parc Sanitari Sant Joan de Déu, CIBERSAM, Teaching, Research and Innovation Unit, Sant Boi de Llobregat, Spain
[8] Hospital Neuropsiquiátrico "Dr. Braulio A. Moyano", Buenos Aires, Argentina

E-mail: novick_diego@lilly.com

Author address:
[1] Health Outcomes
Eli Lilly and Co.
Windlesham
Surrey
UK

Citation: Novick D, Mendez G, Carballido M, Rizzo M, O'Connor JM, Castillo J, et al. Retrospective analysis of patients with locally advanced or metastatic gastric cancer in Argentina. Medwave 2019;19(8):e7692 doi: 10.5867/medwave.2019.08.7692

Submission date: 12/12/2018

Acceptance date: 22/7/2019

Publication date: 24/9/2019

Origin: not commissioned

Type of review: Peer-reviewed by four external reviewers, double blind

PubMed record

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1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. | CrossRef | PubMed |
2. Piazuelo M blanca, Correa P. Gastric cancer: Overview. Colomb Med. 2013;44: 192–201. | Link |
3. Torpy JM, Lynm C, Glass RM. JAMA patient page. Stomach cancer. JAMA. 2010 May 5;303(17):1771. | CrossRef | PubMed |
4. Atlas de mortalidad por cáncer. Argentina 2011-2015 – Instituto Nacional del Cáncer [on line]. | Link |
5. Global Burden of Disease. Institute of Health Metrics and Evaluation [on line]. | Link |
6. International Organization for Migration. Migration trends in South America, South American Migration Reports No. 1, 2017. The UN Migration Agency. [on line] | Link |
7. Bang YJ, Yalcin S, Roth A, Hitier S, Ter-Ovanesov M, Wu CW, et al. Registry of gastric cancer treatment evaluation (REGATE): I base-line disease characteristics. Asia Pac J Clin Oncol. 2014 Mar;10(1):38-52. | CrossRef | PubMed |
8. Kim R, Tan A, Choi M, El-Rayes BF. Geographic differences in approach to advanced gastric cancer: Is there a standard approach? Crit Rev Oncol Hematol. 2013 Nov;88 2):416-26. | CrossRef | PubMed |
9. Bauer K, Schroeder M, Porzsolt F, Henne-Bruns D. Comparison of international guidelines on the accompanying therapy for advanced gastric cancer: reasons for the differences. J Gastric Cancer. 2015 Mar;15(1):10-8. | CrossRef | PubMed |
10. Digklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016 Feb 28;22(8):2403-14. | CrossRef | PubMed |
11. Janowitz T, Thuss-Patience P, Marshall A, Kang JH, Connell C, Cook N, et al. Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data. Br J Cancer. 2016 Feb 16;114(4):381-7. | CrossRef | PubMed |
12. Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology. JNCCN Journal of the National Comprehensive Cancer Network, 14(10), 1286-1312. | CrossRef |
13. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v38-v49. | PubMed |
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16. López-Moncayo H, Ospina-Nieto J, Rubiano-Vinueza J, Rey-Ferro M. Gastric Cancer. Surgical Management Guidelines 2009.Guia de manejo en Cirugia; 2009. | Link |
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18. Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997 Feb;8(2):163-8. | CrossRef | PubMed |
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20. Cassidy J, Saltz L, Twelves C, Van Cutsem E, Hoff P, Kang Y, et al. Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients. Ann Oncol. 2011 Dec;22(12):2604-9. | CrossRef | PubMed |
21. Aguado C, García-Paredes B, Sotelo MJ, Sastre J, Díaz-Rubio E. Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer? World J Gastroenterol. 2014 May 28;20(20):6092-101. | CrossRef | PubMed |
22. 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 Sep;20(9):1529-34. | CrossRef | PubMed |
23. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto 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 Jan;26(1):141-8. | CrossRef | PubMed |
24. Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al. 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 Mar 20;26(9):1435-42. | CrossRef | PubMed |
25. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. | CrossRef | PubMed |
26. Starling N, Rao S, Cunningham D, Iveson T, Nicolson M, Coxon F, et al. Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J Clin Oncol. 2009 Aug 10;27(23):3786-93. | CrossRef | PubMed |
27. Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, 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 Aug;19(8):1450-7. | CrossRef | PubMed |
28. Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, et al. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. | CrossRef | PubMed |
29. Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. | CrossRef | PubMed |
30. Shi J, Gao P, Song Y, Chen X, Li Y, Zhang C, et al. Efficacy and safety of taxane-based systemic chemotherapy of advanced gastric cancer: A systematic review and meta-analysis. Sci Rep. 2017 Jul 13;7(1):5319. | CrossRef | PubMed |
31. Apicella M, Corso S, Giordano S. Targeted therapies for gastric cancer: failures and hopes from clinical trials. Oncotarget. 2017 Jan 26;8(34):57654-57669. | CrossRef | PubMed |
32. Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, 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 Oct;47(15):2306-14. | CrossRef | PubMed |
33. Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma(COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. | CrossRef | PubMed |
34. Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, 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 May 1;30(13):1513-8. | CrossRef | PubMed |
35. Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, et al. 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 Jun;24(6):1567-73. | CrossRef | PubMed |
36. 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 Mar;9(3):215-21. | CrossRef | PubMed |
37. Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, et al. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. | CrossRef | PubMed |
38. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. | CrossRef | PubMed |
39. Yamaguchi K, Shimamura T, Hyodo I, Koizumi W, Doi T, Narahara H, et al. Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer. Br J Cancer. 2006 Jun 19;94(12):1803-8. | CrossRef | PubMed |
40. 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 V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. | PubMed |
41. Wang Y, Yu YY, Li W, Feng Y, Hou J, Ji Y, et al. A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis. Cancer Chemother Pharmacol. 2014 Jun;73(6):1155-61. | CrossRef | PubMed |
42. Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol. 2009 Dec;16(12):3227-36. | CrossRef | PubMed |
43. Suzuki T, Tanabe K, Taomoto J, Yamamoto H, Tokumoto N, Yoshida K, et al. Preliminary trial of adjuvant surgery for advanced gastric cancer. Oncol Lett. 2010 Jul;1(4):743-747. Epub 2010 Jul 1. | CrossRef | PubMed |
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Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. | CrossRef | PubMed |

Piazuelo M blanca, Correa P. Gastric cancer: Overview. Colomb Med. 2013;44: 192–201. | Link |

Torpy JM, Lynm C, Glass RM. JAMA patient page. Stomach cancer. JAMA. 2010 May 5;303(17):1771. | CrossRef | PubMed |

Atlas de mortalidad por cáncer. Argentina 2011-2015 – Instituto Nacional del Cáncer [on line]. | Link |

Global Burden of Disease. Institute of Health Metrics and Evaluation [on line]. | Link |

International Organization for Migration. Migration trends in South America, South American Migration Reports No. 1, 2017. The UN Migration Agency. [on line] | Link |

Bang YJ, Yalcin S, Roth A, Hitier S, Ter-Ovanesov M, Wu CW, et al. Registry of gastric cancer treatment evaluation (REGATE): I base-line disease characteristics. Asia Pac J Clin Oncol. 2014 Mar;10(1):38-52. | CrossRef | PubMed |

Kim R, Tan A, Choi M, El-Rayes BF. Geographic differences in approach to advanced gastric cancer: Is there a standard approach? Crit Rev Oncol Hematol. 2013 Nov;88 2):416-26. | CrossRef | PubMed |

Bauer K, Schroeder M, Porzsolt F, Henne-Bruns D. Comparison of international guidelines on the accompanying therapy for advanced gastric cancer: reasons for the differences. J Gastric Cancer. 2015 Mar;15(1):10-8. | CrossRef | PubMed |

Digklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol. 2016 Feb 28;22(8):2403-14. | CrossRef | PubMed |

Janowitz T, Thuss-Patience P, Marshall A, Kang JH, Connell C, Cook N, et al. Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data. Br J Cancer. 2016 Feb 16;114(4):381-7. | CrossRef | PubMed |

Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric Cancer, Version 3.2016; Clinical Practice Guidelines in Oncology. JNCCN Journal of the National Comprehensive Cancer Network, 14(10), 1286-1312. | CrossRef |

Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v38-v49. | PubMed |

Kodera Y, Sano T. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20:1-19. | CrossRef | Link |

Speroni A, Fantana M, Boffi-Boggero H, García C, Foglia V. Epidemiología descriptiva del cáncer digestivo en 708 casos. Argentina 1992. Boletín la Acad Nac Med Buenos Aires. 1993;71: 517-29.

López-Moncayo H, Ospina-Nieto J, Rubiano-Vinueza J, Rey-Ferro M. Gastric Cancer. Surgical Management Guidelines 2009.Guia de manejo en Cirugia; 2009. | Link |

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: 2903-2909. | CrossRef |

Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997 Feb;8(2):163-8. | CrossRef | PubMed |

Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, et al. 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 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. | CrossRef | PubMed |

Cassidy J, Saltz L, Twelves C, Van Cutsem E, Hoff P, Kang Y, et al. Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients. Ann Oncol. 2011 Dec;22(12):2604-9. | CrossRef | PubMed |

Aguado C, García-Paredes B, Sotelo MJ, Sastre J, Díaz-Rubio E. Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer? World J Gastroenterol. 2014 May 28;20(20):6092-101. | CrossRef | PubMed |

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 Sep;20(9):1529-34. | CrossRef | PubMed |

Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto 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 Jan;26(1):141-8. | CrossRef | PubMed |

Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al. 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 Mar 20;26(9):1435-42. | CrossRef | PubMed |

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. | CrossRef | PubMed |

Starling N, Rao S, Cunningham D, Iveson T, Nicolson M, Coxon F, et al. Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J Clin Oncol. 2009 Aug 10;27(23):3786-93. | CrossRef | PubMed |

Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, 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 Aug;19(8):1450-7. | CrossRef | PubMed |

Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, et al. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. | CrossRef | PubMed |

Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. | CrossRef | PubMed |

Shi J, Gao P, Song Y, Chen X, Li Y, Zhang C, et al. Efficacy and safety of taxane-based systemic chemotherapy of advanced gastric cancer: A systematic review and meta-analysis. Sci Rep. 2017 Jul 13;7(1):5319. | CrossRef | PubMed |

Apicella M, Corso S, Giordano S. Targeted therapies for gastric cancer: failures and hopes from clinical trials. Oncotarget. 2017 Jan 26;8(34):57654-57669. | CrossRef | PubMed |

Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, 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 Oct;47(15):2306-14. | CrossRef | PubMed |

Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma(COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. | CrossRef | PubMed |

Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, 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 May 1;30(13):1513-8. | CrossRef | PubMed |

Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, et al. 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 Jun;24(6):1567-73. | CrossRef | PubMed |

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 Mar;9(3):215-21. | CrossRef | PubMed |

Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, et al. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. | CrossRef | PubMed |

Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. | CrossRef | PubMed |

Yamaguchi K, Shimamura T, Hyodo I, Koizumi W, Doi T, Narahara H, et al. Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer. Br J Cancer. 2006 Jun 19;94(12):1803-8. | CrossRef | PubMed |

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 V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. | PubMed |

Wang Y, Yu YY, Li W, Feng Y, Hou J, Ji Y, et al. A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis. Cancer Chemother Pharmacol. 2014 Jun;73(6):1155-61. | CrossRef | PubMed |

Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol. 2009 Dec;16(12):3227-36. | CrossRef | PubMed |

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