Safety and feasibility of adjuvant chemotherapy with S-1 for Korean patients with curatively resected advanced gastric cancer
Adjuvant chemotherapy with S-1 was proven to be effective in Japanese patients with advanced gastric cancer curatively resected with D2 lymph node dissection.
Materials and methods
We retrospectively evaluated the medical records of 305 patients with stage II, III or IV (M0) gastric cancer who had received adjuvant S-1 chemotherapy following curative gastrectomy with D2 lymph node dissection between October 2007 and December 2009. Adjuvant S-1 was administered at a dose of 40 mg/m2 twice daily for 4 weeks followed by 2 weeks of rest, every 6 weeks for eight cycles.
Of the 305 patients, 248 (81.3 %) and 198 (64.9 %) completed four and eight cycles of adjuvant chemotherapy, respectively. The most common reasons for discontinuing treatment prior to the planned eight cycles were adverse events (n = 47, 15.4 %) and tumor recurrence (n = 28, 9.2 %). Sixty-five (21.3 %) patients required dose reduction due to adverse events. The most common grade 3/4 toxicities were neutropenia (n = 39, 12.8 %), diarrhea (n = 15, 4.9 %). Multivariate analysis showed that total gastrectomy [odds ratio (OR) 2.44; 95 % confidence interval (CI) 1.29–4.62, p = 0.006] was an independent risk factor for grade 3/4 hematologic toxicities, and age > 65 years (OR 2.60; 95 % CI 1.34–5.07, p = 0.005) was an independent risk factor for grade 3 non-hematologic toxicities.
Adjuvant chemotherapy with S-1 for 1 year is safe and feasible in Korean patients. Age > 65 years and total gastrectomy are independent risk factors for severe adverse events caused by adjuvant S-1 chemotherapy.
KeywordsGastric cancer Adjuvant Chemotherapy S-1
- 5.Mari E, Floriani I, Tinazzi A, Buda A, Belfiglio M, Valentini M, Cascinu S, Barni S, Labianca R, Torri V (2000) Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente). Ann Oncol 11(7):837–843PubMedCrossRefGoogle Scholar
- 8.Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345(10):725–730. doi:10.1056/NEJMoa010187 PubMedCrossRefGoogle Scholar
- 9.Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, Participants MT (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20. doi:10.1056/NEJMoa055531 PubMedCrossRefGoogle Scholar
- 10.Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357(18):1810–1820. doi:10.1056/NEJMoa072252 PubMedCrossRefGoogle Scholar
- 11.Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Ji J, Yeh TS, Button P, Sirzen F, Noh SH (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. doi:10.1016/S0140-6736(11)61873-4 PubMedGoogle Scholar
- 12.Kang Y, Chang H, Zang D, Lee J, Kim T, Yang D, Jang S, Yook J, Oh S, Kim B (2008) Postoperative adjuvant chemotherapy for grossly serosa-positive advanced gastric cancer: A randomized phase III trial of intraperitoneal cisplatin and early mitomycin-C plus long-term doxifluridine plus cisplatin (iceMFP) versus mitomycin-C plus short- term doxifluridine (Mf) (AMC 0101) (NCT00296322). J Clin Oncol 26 (May 20 suppl; abstr LBA4511)Google Scholar
- 13.Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M (1996) Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 7(5):548–557PubMedCrossRefGoogle Scholar
- 15.Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13(3):176–181. doi:10.1016/S1053-4296(03)00031-6 PubMedCrossRefGoogle Scholar
- 16.Kinoshita T, Nashimoto A, Yamamura Y, Okamura T, Sasako M, Sakamoto J, Kojima H, Hiratsuka M, Arai K, Sairenji M, Fukushima N, Kimura H, Nakajima T (2004) Feasibility study of adjuvant chemotherapy with S-1 (TS-1; tegafur, gimeracil, oteracil potassium) for gastric cancer. Gastric Cancer 7(2):104–109. doi:10.1007/s10120-004-0278-3 PubMedCrossRefGoogle Scholar
- 18.Iwasa S, Yamada Y, Fukagawa T, Eguchi Nakajima T, Kato K, Hamaguchi T, Morita S, Saka M, Katai H, Shimada Y (2011) Management of adjuvant S-1 therapy after curative resection of gastric cancer: dose reduction and treatment schedule modification. Gastric Cancer 14(1):28–34. doi:10.1007/s10120-011-0003-y PubMedCrossRefGoogle Scholar
- 21.Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M (2008) Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3,758 patients. Cancer Chemother Pharmacol 61(2):335–343. doi:10.1007/s00280-007-0595-4 PubMedCrossRefGoogle Scholar
- 22.Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, Tatsuta M, Kawasaki T, Satomi T (2002) Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function. Cancer Chemother Pharmacol 50(1):25–32. doi:10.1007/s00280-002-0457-z PubMedCrossRefGoogle Scholar