Journal of Gastric Cancer

  • 제17권2호
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  • Pages.120-131
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  • 2017
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  • 2093-582X(pISSN)
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  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
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Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial

  • Kim, Young-Il (Center for Gastric Cancer, National Cancer Center) ;
  • Kim, Mi-Jung (Center for Gastric Cancer, National Cancer Center) ;
  • Park, Sook Ryun (Center for Gastric Cancer, National Cancer Center) ;
  • Kim, Hark Kyun (Center for Gastric Cancer, National Cancer Center) ;
  • Cho, Soo-Jeong (Center for Gastric Cancer, National Cancer Center) ;
  • Lee, Jong Yeul (Center for Gastric Cancer, National Cancer Center) ;
  • Kim, Chan Gyoo (Center for Gastric Cancer, National Cancer Center) ;
  • Kim, Gwang Ha (Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital) ;
  • Park, Moo In (Department of Internal Medicine, Kosin University College of Medicine) ;
  • Nam, Byung-Ho (Biometric Research Branch, Research Institute for National Cancer Control & Evaluation, National Cancer Center) ;
  • Park, Young Iee (Center for Gastric Cancer, National Cancer Center) ;
  • Choi, Il Ju (Center for Gastric Cancer, National Cancer Center)
  • 투고 : 2017.04.09
  • 심사 : 2017.05.08
  • 발행 : 2017.06.30
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초록

Purpose: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. Materials and Methods: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). Results: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. Conclusions: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

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참고문헌

  1. Savides TJ, Jensen DM, Cohen J, Randall GM, Kovacs TO, Pelayo E, et al. Severe upper gastrointestinal tumor bleeding: endoscopic findings, treatment, and outcome. Endoscopy 1996;28:244-248. https://doi.org/10.1055/s-2007-1005436
  2. Sheibani S, Kim JJ, Chen B, Park S, Saberi B, Keyashian K, et al. Natural history of acute upper GI bleeding due to tumours: short-term success and long-term recurrence with or without endoscopic therapy. Aliment Pharmacol Ther 2013;38:144-150. https://doi.org/10.1111/apt.12347
  3. Loftus EV Jr, Alexander GL, Ahlquist DA, Balm RK. Endoscopic treatment of major bleeding from advanced gastroduodenal malignant lesions. Mayo Clin Proc 1994;69:736-740. https://doi.org/10.1016/S0025-6196(12)61090-8
  4. Kim YI, Choi IJ, Cho SJ, Lee JY, Kim CG, Kim MJ, et al. Outcome of endoscopic therapy for cancer bleeding in patients with unresectable gastric cancer. J Gastroenterol Hepatol 2013;28:1489-1495. https://doi.org/10.1111/jgh.12262
  5. Koh KH, Kim K, Kwon DH, Chung BS, Sohn JY, Ahn DS, et al. The successful endoscopic hemostasis factors in bleeding from advanced gastric cancer. Gastric Cancer 2013;16:397-403. https://doi.org/10.1007/s10120-012-0200-3
  6. Neumann I, Letelier LM, Rada G, Claro JC, Martin J, Howden CW, et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2013:CD007999.
  7. Lau JY, Leung WK, Wu JC, Chan FK, Wong VW, Chiu PW, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007;356:1631-1640. https://doi.org/10.1056/NEJMoa065703
  8. Lau JY, Sung JJ, Lee KK, Yung MY, Wong SK, Wu JC, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med 2000;343:310-316. https://doi.org/10.1056/NEJM200008033430501
  9. Chan FK, Wong VW, Suen BY, Wu JC, Ching JY, Hung LC, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet 2007;369:1621-1626. https://doi.org/10.1016/S0140-6736(07)60749-1
  10. Lai KC, Lam SK, Chu KM, Wong BC, Hui WM, Hu WH, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-2038. https://doi.org/10.1056/NEJMoa012877
  11. Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015;47:a1-a46. https://doi.org/10.1055/s-0034-1393172
  12. Hwang JH, Fisher DA, Ben-Menachem T, Chandrasekhara V, Chathadi K, Decker GA, et al. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc 2012;75:1132-1138. https://doi.org/10.1016/j.gie.2012.02.033
  13. Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974;2:394-397.
  14. Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988;16:1141-1154. https://doi.org/10.1214/aos/1176350951
  15. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496-509. https://doi.org/10.1080/01621459.1999.10474144
  16. Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ 2005;330:568. https://doi.org/10.1136/bmj.38356.641134.8F
  17. Lanas A, Garcia-Rodriguez LA, Arroyo MT, Bujanda L, Gomollon F, Forne M, et al. Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007;102:507-515. https://doi.org/10.1111/j.1572-0241.2006.01062.x
  18. Kim YI, Choi IJ. Endoscopic management of tumor bleeding from inoperable gastric cancer. Clin Endosc 2015;48:121-127. https://doi.org/10.5946/ce.2015.48.2.121
  19. Laine L, Shah A, Bemanian S. Intragastric pH with oral vs intravenous bolus plus infusion proton-pump inhibitor therapy in patients with bleeding ulcers. Gastroenterology 2008;134:1836-1841. https://doi.org/10.1053/j.gastro.2008.03.006
  20. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38-43.
  21. Sakita T, Oguro Y, Takasu S, Fukutomi H, Miwa T. Observations on the healing of ulcerations in early gastric cancer. The life cycle of the malignant ulcer. Gastroenterology 1971;60:835-839.
  22. Myung YS, Hong SJ, Han JP, Park KW, Ko BM, Lee MS. Effects of administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer. Gastric Cancer 2017;20:200-206. https://doi.org/10.1007/s10120-015-0578-9
  23. Imbesi JJ, Kurtz RC. A multidisciplinary approach to gastrointestinal bleeding in cancer patients. J Support Oncol 2005;3:101-110.
  24. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;372:1832-1843. https://doi.org/10.1056/NEJMra1401038
  25. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2010:CD004064.
  26. 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;376:687-697. https://doi.org/10.1016/S0140-6736(10)61121-X
  27. Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, 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;29:3968-3976. https://doi.org/10.1200/JCO.2011.36.2236
  28. Suh M, Choi KS, Park B, Lee YY, Jun JK, Lee DH, et al. Trends in cancer screening rates among Korean men and women: results of the Korean National Cancer Screening Survey, 2004-2013. Cancer Res Treat 2016;48:1-10. https://doi.org/10.4143/crt.2014.204
  29. Kim YG, Kong SH, Oh SY, Lee KG, Suh YS, Yang JY, et al. Effects of screening on gastric cancer management: comparative analysis of the results in 2006 and in 2011. J Gastric Cancer 2014;14:129-134. https://doi.org/10.5230/jgc.2014.14.2.129
  30. Kim HS, Lee H, Jeung HC, Noh SH, Chung HC, Roh JK, et al. Advanced detection of recent changing trends in gastric cancer survival: up-to-date comparison by period analysis. Jpn J Clin Oncol 2011;41:1344-1350. https://doi.org/10.1093/jjco/hyr153
  31. Kim SM, Park SH. Chemotherapy beyond second-line in advanced gastric cancer. World J Gastroenterol 2015;21:8811-8816. https://doi.org/10.3748/wjg.v21.i29.8811

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