Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11
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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.
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.
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%).
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.
ClinicalTrials.gov Identifier: NCT02527785.
KeywordsStomach neoplasm Irinotecan Oxaliplatin S-1 Phase II clinical trial
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.
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.
- 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.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
- 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
- 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
- 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.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.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
- 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.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