Journal of Gastric Cancer

  • 제23권2호
  • /
  • Pages.315-327
  • /
  • 2023
  • /
  • 2093-582X(pISSN)
  • /
  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
권호 표지
DOI QR코드

DOI QR Code

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation

  • Guk Jin Lee (Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Hyunho Kim (Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sung Shim Cho (Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Hyung Soon Park (Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Ho Jung An (Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea) ;
  • In Sook Woo (Division of Medical Oncology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jae Ho Byun (Division of Medical Oncology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Ji Hyung Hong (Division of Medical Oncology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Yoon Ho Ko (Division of Medical Oncology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Der Sheng Sun (Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Hye Sung Won (Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jong Youl Jin (Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Ji Chan Park (Division of Medical Oncology, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • In-Ho Kim (Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sang Young Roh (Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Byoung Yong Shim (Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea)
  • 투고 : 2022.08.22
  • 심사 : 2023.02.09
  • 발행 : 2023.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

키워드

과제정보

The authors thank all patients and investigators who participated in this study. We also thank Roche, Ltd. (Korea) for supplying the capecitabine.

참고문헌

  1. Faivre J, Forman D, Esteve J, Gatta G; EUROCARE Working Group. Survival of patients with oesophageal and gastric cancers in Europe. Eur J Cancer 1998;34:2167-2175.  https://doi.org/10.1016/S0959-8049(98)00329-3
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.  https://doi.org/10.3322/caac.21254
  3. Muro K, Van Cutsem E, Narita Y, Pentheroudakis G, Baba E, Li J, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol 2019;30:19-33.  https://doi.org/10.1093/annonc/mdy502
  4. Catalano V, Graziano F, Santini D, D'Emidio S, Baldelli AM, Rossi D, et al. Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer 2008;99:1402-1407.  https://doi.org/10.1038/sj.bjc.6604732
  5. 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;358:36-46.  https://doi.org/10.1056/NEJMoa073149
  6. 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;9:215-221.  https://doi.org/10.1016/S1470-2045(08)70035-4
  7. Carter GC, Kaltenboeck A, Ivanova J, Liepa AM, San Roman A, Koh M, et al. Real-world treatment patterns among patients with advanced gastric cancer in South Korea. Cancer Res Treat 2017;49:578-587.  https://doi.org/10.4143/crt.2016.001
  8. Eren OO, Ozturk MA, Sonmez OU, Oyan B. Safety, feasibility, and efficacy of capecitabine maintenance in patients with advanced gastric cancer: a retrospective study. Am J Ther 2016;23:e1493-e1497.  https://doi.org/10.1097/MJT.0000000000000156
  9. Qiu MZ, Wei XL, Zhang DS, Jin Y, Zhou YX, Wang DS, et al. Efficacy and safety of capecitabine as maintenance treatment after first-line chemotherapy using oxaliplatin and capecitabine in advanced gastric adenocarcinoma patients: a prospective observation. Tumour Biol 2014;35:4369-4375.  https://doi.org/10.1007/s13277-013-1574-5
  10. Yao Y, Deng R, Liao D, Xie H, Zuo J, Jia Y, et al. Maintenance treatment in advanced HER2-negative gastric cancer. Clin Transl Oncol 2020;22:2206-2212.  https://doi.org/10.1007/s12094-020-02379-7
  11. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 2021;24:1-21.  https://doi.org/10.1007/s10120-020-01042-y
  12. Park YH, Lee JL, Ryoo BY, Ryu MH, Yang SH, Kim BS, et al. Capecitabine in combination with oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol 2008;61:623-629.  https://doi.org/10.1007/s00280-007-0515-7
  13. Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797-805.  https://doi.org/10.1111/j.1365-2559.2008.03028.x
  14. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247.  https://doi.org/10.1016/j.ejca.2008.10.026
  15. Liu YJ, Zhu GP, Guan XY. Comparison of the NCI-CTCAE version 4.0 and version 3.0 in assessing chemoradiation-induced oral mucositis for locally advanced nasopharyngeal carcinoma. Oral Oncol 2012;48:554-559.  https://doi.org/10.1016/j.oraloncology.2012.01.004
  16. Lakatos E. Sample sizes based on the log-rank statistic in complex clinical trials. Biometrics 1988;44:229-241.  https://doi.org/10.2307/2531910
  17. Shitara K, Ikeda J, Yokota T, Takahari D, Ura T, Muro K, et al. Progression-free survival and time to progression as surrogate markers of overall survival in patients with advanced gastric cancer: analysis of 36 randomized trials. Invest New Drugs 2012;30:1224-1231.  https://doi.org/10.1007/s10637-011-9648-y
  18. Chibaudel B, Maindrault-Goebel F, Lledo G, Mineur L, Andre T, Bennamoun M, et al. Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 2009;27:5727-5733. https://doi.org/10.1200/JCO.2009.23.4344
  19. Waddell T, Gollins S, Soe W, Valle J, Allen J, Bentley D, et al. Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by maintenance capecitabine in advanced colorectal cancer: XelQuali study. Cancer Chemother Pharmacol 2011;67:1111-1117.  https://doi.org/10.1007/s00280-010-1322-0
  20. Roviello G, Rodriquenz MG, Aprile G, D'Angelo A, Roviello F, Nobili S, et al. Maintenance in gastric cancer: new life for an old issue? Crit Rev Oncol Hematol 2021;160:103307. 
  21. Petrioli R, Francini E, Roviello F, Marrelli D, Miano ST, Fiaschi AI, et al. Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged ≥ 75 years with impaired performance status. J Geriatr Oncol 2015;6:380-386.  https://doi.org/10.1016/j.jgo.2015.06.002
  22. Park SR, Kim MJ, Nam BH, Kim CG, Lee JY, Cho SJ, et al. A randomised phase II study of continuous versus stop-and-go S-1 plus oxaliplatin following disease stabilisation in first-line chemotherapy in patients with metastatic gastric cancer. Eur J Cancer 2017;83:32-42.  https://doi.org/10.1016/j.ejca.2017.06.008
  23. Lu B, Bao LB, Sun Z, Hua ZL, Wang X, Qu CP. Efficacy and safety of capecitabine as maintenance therapy after capecitabine-based combination chemotherapy for patients with advanced esophagogastric junction adenocarcinoma. Eur Rev Med Pharmacol Sci 2015;19:3605-3612. 
  24. Haag GM, Stocker G, Quidde J, Jaeger D, Lordick F. Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer - the multinational MATEO study. BMC Cancer 2017;17:509. 
  25. Haag GM, Stocker G, Lorenzen S, Ettrich TJ, Longo F, Kiani A, et al. 1447P S-1 maintenance therapy in non-Asian patients with advanced, HER-2 negative esophagogastric adenocarcinoma - first results of the international MATEO trial initiated by the AIO. Ann Oncol 2020;31:S910. 
  26. Moehler M, Dvorkin M, Boku N, Ozguroglu M, Ryu MH, Muntean AS, et al. Phase III trial of avelumab maintenance after first-line induction chemotherapy versus continuation of chemotherapy in patients with gastric cancers: results from JAVELIN Gastric 100. J Clin Oncol 2021;39:966-977. https://doi.org/10.1200/JCO.20.00892