Adjuvant chemotherapy is an accepted treatment to improve survival rates in patients with stage III colon cancer, and regimens including oxaliplatin have been shown to be superior to those containing 5-FU alone. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) as adjuvant chemotherapy for patients with stage III colon cancer following curative resection.
Patients with colon cancer who underwent curative resection were enrolled and received oral S-1 40–60 mg twice daily on days 1–14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for eight courses. The primary endpoint was 3-year disease-free survival rate. Secondary endpoints were the rate of treatment completion, adverse events, relative dose intensity, and overall survival.
Between February 2014 and December 2014, 89 patients were enrolled. One patient was excluded from the analysis because of ineligibility, and the remaining 88 patients were included. The rate of protocol treatment completion was 72.3%. The relative dose intensity of S-1 and oxaliplatin was 72% and 76.3%, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). The incidence of grade 2 neuropathy has decreased from 8.1 to 2.7% after 3 years of the therapy. Three-year disease-free survival rate was 73.9% (95% CI 63.8–81.9), and 3-year overall survival rate was 94.3% (95% CI 86.8–97.6)
C-SOX is a safe and feasible adjuvant chemotherapy regimen in patients with stage III colon cancer undergoing curative resection.
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Andre T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://doi.org/10.1056/NEJMoa032709
Andre T, Boni C, Navarro M et al (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27(19):3109–3116. https://doi.org/10.1200/JCO.2008.20.6771
Andre T, de Gramont A, Vernerey D et al (2015) Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol 33(35):4176–4187. https://doi.org/10.1200/JCO.2015.63.4238
Haller DG, Tabernero J, Maroun J et al (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29(11):1465–1471. https://doi.org/10.1200/JCO.2010.33.6297
Kuebler JP, Colangelo L, O'Connell MJ et al (2007) Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin: a prospective analysis. Cancer 110(9):1945–1950. https://doi.org/10.1002/cncr.23013
Grothey A, Sobrero AF, Shields AF et al (2018) Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med 378(13):1177–1188. https://doi.org/10.1056/NEJMoa1713709
Shirasaka T, Shimamato Y, Ohshimo H et al (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):548–557
Yamada Y, Takahari D, Matsumoto H et al (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14(13):1278–1286. https://doi.org/10.1016/S1470-2045(13)70490-X
Hong YS, Park YS, Lim HY et al (2012) S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol 13(11):1125–1132. https://doi.org/10.1016/S1470-2045(12)70363-7
Hamaguchi T, Shimada Y, Mizusawa J et al (2018) Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. Lancet Gastroenterol Hepatol 3(1):47–56. https://doi.org/10.1016/S2468-1253(17)30297-2
Andre T, Iveson T, Labianca R et al (2013) The IDEA (International duration evaluation of adjuvant chemotherapy) collaboration: prospective combined analysis of phase III trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or modified FOLFOX6) or XELOX (3 versus 6 months) regimen for patients with stage III colon cancer: trial design and current status. Curr Colorect Cancer Rep 9:261–269. https://doi.org/10.1007/s11888-013-0181-6
Yoshino T, Yamanaka T, Oki E et al (2019) Efficacy and long-term peripheral sensory neuropathy of 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer: the ACHIEVE phase 3 randomized clinical trial. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.2572
Kotaka M, Yamanaka T, Yoshino T et al (2018) Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer. ESMO Open 3(3):e000354. https://doi.org/10.1136/esmoopen-2018-000354
Sobrero A, Grothey A, Iveson T et al (2018) The hard road to data interpretation: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer? Ann Oncol 29(5):1099–1107. https://doi.org/10.1093/annonc/mdy064
We thank Clare Cox, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Conflict of interest
This study was funded by Yakult Honsha Co., Ltd.
The ethical, medical, and scientific aspects of this study were reviewed and approved by the ethics committee of each participating institution in the University Hospital Medical Information Network (UMIN) clinical trials registry (UMIN000012618). The study was conducted in accordance with the principles of the Declaration of Helsinki. This study was approved by the Ethics Committees of the participating institutions and registered in the UMIN clinical trials registry (UMIN000012618).
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Ando, K., Emi, Y., Miyanari, N. et al. Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for treating patients with stage III colon cancer (KSCC1303): final analysis of 3-year disease-free survival. Int J Clin Oncol 25, 1115–1122 (2020). https://doi.org/10.1007/s10147-020-01646-5
- Adjuvant chemotherapy
- Stage III colon cancer
- Multicenter single-arm open-label prospective phase II clinical trial