Advertisement

Gastric Cancer

, Volume 21, Issue 5, pp 802–810 | Cite as

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11

  • Hyeong Su Kim
  • Min-Hee Ryu
  • Dae Young Zang
  • Sook Ryun Park
  • Boram Han
  • Won Ki Kang
  • Sun Young Rha
  • Minkyu Jung
  • Jin-Soo Kim
  • Byung Woog Kang
  • Kyung-Hee Lee
  • Sang-Young Rho
  • Jung Han Kim
  • Kab Choong Kim
  • Ji Woong Cho
  • Dae Ro Choi
  • Hyun Lim
  • Ho Suk Kang
  • Jae Seung Soh
  • Min-Jeong Kim
  • Jinwon Seo
  • Yoon-Koo Kang
Original Article
  • 428 Downloads

Abstract

Background

Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer.

Methods

Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1–7 of every 2-week cycle.

Results

Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1–31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6–74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6–14.0) and 15.4 months (95% CI 12.6–18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%).

Conclusion

These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice.

Trial Registration

ClinicalTrials.gov Identifier: NCT02527785.

Keywords

Stomach neoplasm Irinotecan Oxaliplatin S-1 Phase II clinical trial 

Notes

Acknowledgements

This research was supported by a Hallym University Research Fund (HURF-2015-38),Anyang-si, Korea, and a grant from the Korean Cancer Study Group and KCSG data center (ST14-11), Seoul, Korea and a Grant (15182MFDS512) from Minister of Food and Drug Safety in 2015, Cheongju-si, Korea. Irinotecan and oxaliplatin were generously provided by Hanmi Pharm. Co., Ltd., and S-1 was provided by Jeil Pharmaceutical Co., Ltd.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.

Supplementary material

10120_2018_794_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Jung K, Won Y, Oh C, Kong H, Lee DH, Lee KH. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2014. Cancer Res Treat. 2017;49:292–305.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Power DG, Kelsen DP, Shah MA. Advanced gastric cancer–slow but steady progress. Cancer Treat Rev. 2010;36:384–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;2010:CD004064.Google Scholar
  5. 5.
    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;24:4991–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Amarantidis K, Xenidis N, Chelis L, Chamalidou E, Dimopoulos P, Michailidis P, et al. Docetaxel plus oxaliplatin in combination with capecitabine as first-line treatment for advanced gastric cancer. Oncology. 2011;80:359–65.CrossRefPubMedGoogle Scholar
  7. 7.
    Comella P, Lorusso V, Maiorino L, Casaretti R, Cannone M, Massidda B, et al. Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group. Cancer Chemother Pharmacol. 2009;64:893–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Di Lauro L, Giacinti L, Arena MG, Sergi D, Fattoruso SI, Giannarelli D, et al. Phase II study of epirubicin, oxaliplatin and docetaxel combination in metastatic gastric or gastroesophageal junction adenocarcinoma. J Exp Clin Cancer Res. 2009;28:34.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Iwase H, Shimada M, Tsuzuki T, Ina K, Sugihara M, Haruta J, et al. A phase II multi-center study of triple therapy with paclitaxel, S-1 and cisplatin in patients with advanced gastric cancer. Oncology. 2011;80:76–83.CrossRefPubMedGoogle Scholar
  10. 10.
    Koizumi W, Nakayama N, Tanabe S, Sasaki T, Higuchi K, Nishimura K, et al. A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601). Cancer Chemother Pharmacol. 2012;69:407–13.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim JY, Do YR, Park KU, Kim JG, Chae YS, Kim MK, et al. Multicenter phase II trial of S-1, paclitaxel and cisplatin triplet combination chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol. 2011;67:527–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Van Cutsem E, Boni C, Tabernero J, Massuti B, Middleton G, Dane F, et al. Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gas-tric cancer: a randomized phase II study. Ann Oncol. 2015;26:149–56.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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;10:1063–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Pozzo C, Barone C, Szanto J, Padi E, Peschel C, Bukki J, et al. Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol. 2004;15:1773–81.CrossRefPubMedGoogle Scholar
  16. 16.
    Moehler M, Eimermacher A, Siebler J, Hohler T, Wein A, Menges M, et al. Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer. Br J Cancer. 2005;92:2122–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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;19:1450–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Han B, Jung JY, Kim HS, Cho JW, Kim KC, Lim H, et al. A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer. Cancer Chemother Pharmacol. 2016;78:949–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Park SR, Kong SY, Rhee J, Park YI, Ryu KW, Lee JH, et al. Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol. 2011;22:890–6.CrossRefPubMedGoogle Scholar
  20. 20.
    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-naive patients with advanced gastric cancer. Ann Oncol. 2015;26:141–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S, et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus dcf plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US Gastric Cancer Consortium. J Clin Oncol. 2015;33:3874–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, et al. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016;19:234–44.CrossRefPubMedGoogle Scholar
  23. 23.
    Kim HS, Ryu MH, Zang DY, Ryoo BY, Yang DH, Cho JW, et al. Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer. Gastric Cancer. 2016;19:579–85.CrossRefPubMedGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Hyeong Su Kim
    • 1
  • Min-Hee Ryu
    • 2
  • Dae Young Zang
    • 1
    • 12
  • Sook Ryun Park
    • 2
  • Boram Han
    • 1
  • Won Ki Kang
    • 3
  • Sun Young Rha
    • 4
  • Minkyu Jung
    • 4
  • Jin-Soo Kim
    • 5
  • Byung Woog Kang
    • 6
  • Kyung-Hee Lee
    • 7
  • Sang-Young Rho
    • 8
  • Jung Han Kim
    • 1
  • Kab Choong Kim
    • 9
  • Ji Woong Cho
    • 9
  • Dae Ro Choi
    • 1
  • Hyun Lim
    • 1
  • Ho Suk Kang
    • 1
  • Jae Seung Soh
    • 1
  • Min-Jeong Kim
    • 10
  • Jinwon Seo
    • 11
  • Yoon-Koo Kang
    • 2
  1. 1.Department of Internal MedicineHallym University Medical Center, Hallym University College of MedicineAnyang-siRepublic of Korea
  2. 2.Department of OncologyAsan Medical Center, University of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Department of Internal MedicineSamsung Medical Center, Sungkyunkwan University School of MedicineSeoulRepublic of Korea
  4. 4.Department of Medical OncologyYonsei Cancer Center, College of Medicine Yonsei UniversitySeoulRepublic of Korea
  5. 5.Department of Internal MedicineSeoul National University Boramae Medical CenterSeoulRepublic of Korea
  6. 6.Department of Oncology/HematologyKyungpook National University Medical Center, Kyungpook National University School of MedicineDaeguRepublic of Korea
  7. 7.Department of Hematology-OncologyYeungnam University Medical CenterDaeguRepublic of Korea
  8. 8.Department of Internal MedicineSeoul St. Mary’s Hospital, The Catholic University of Korea College of MedicineSeoulRepublic of Korea
  9. 9.Department of SurgeryHallym University Medical Center, Hallym University College of MedicineAnyang-siRepublic of Korea
  10. 10.Department of RadiologyHallym University Medical Center, Hallym University College of MedicineAnyang-siRepublic of Korea
  11. 11.Department of PathologyHallym University Medical Center, Hallym University College of MedicineAnyang-siRepublic of Korea
  12. 12.Division of Hematology-Oncology, Department of Internal MedicineHallym University Medical Center, Hallym University College of MedicineAnyang-siRepublic of Korea

Personalised recommendations