Abstract
Background
A 4-week administration of tegafur/gimeracil/oteracil (S-1) followed by a 2-week rest is the standard adjuvant chemotherapy for surgically resected advanced gastric cancer. This study aimed to evaluate the oncological feasibility of a 2-week S-1 administration followed by a 1-week rest, which is frequently applied in clinical practice to reduce toxicity and improve drug adherence.
Methods
We retrospectively enrolled patients with stage II/III gastric cancer who received S-1 adjuvant chemotherapy following radical gastrectomy from 2006 to 2016 in three institutions. Two-week and 4-week regimen cohorts were compared for relative dose intensity (RDI) as a primary outcome, and treatment completion rate, adverse event incidence, overall survival (OS), and relapse-free survival (RFS) as secondary outcomes. Confounders were adjusted for using propensity score matching (PSM).
Results
One hundred and thirty-four patients received the 2-week regimen and 121 patients received the 4-week regimen. Ninety-five patients were extracted from each group after PSM. The RDIs of S-1 in the 2-week and 4-week cohorts were 73.5 and 69.9%, respectively (p = 0.35), which were not significantly different. The treatment completion rate (54.7 vs. 53.7%, p = 1.0), incidence of grade ≥3 adverse events (7.4 vs. 12.6%, p = 0.33), 3-year OS (76.4 vs. 82.7%, p = 0.78), and 3-year RFS (71.3 vs. 73.4%, p = 0.70) did not significantly differ between both cohorts.
Conclusions
The 2-week S-1 adjuvant chemotherapy could not improve drug adherence in terms of RDI, but its relapse rates were not significantly different compared with those of the 4-week regimen. The 2-week regimen might be considered as an option depending on the patient’s status.
Similar content being viewed by others
References
Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820
Japanease Gastric Cancer Association (2017) Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 20:1–19
Iwasa S, Yamada Y, Fukagawa T et al (2011) Management of adjuvant S-1 therapy after curative resection of gastric cancer: dose reduction and treatment schedule modification. Gastric Cancer 14:28–34
Tsujimoto H, Horiguchi H, Hiraki S et al (2012) Tolerability of adjuvant chemotherapy with S-1 after curative resection in patients with stage II/III gastric cancer. Oncol Lett 4:1135–1139
Kim SJ, Kim YJ, Kim JH et al (2013) Safety, compliance, and predictive parameters for dosage modification in adjuvant S-1 chemotherapy for gastric cancer. Cancer Sci 104:116–123
Kawazoe H, Shimasaki M, Ueno M et al (2015) Risk factors for discontinuation of S-1 adjuvant chemotherapy for gastric cancer. J Cancer 6:464–469
Yoshida K, Kodera Y, Kochi M et al (2019) Addition of docetaxel to oral fluoropyrimidine improves efficacy in patients with stage III gastric cancer: Interim analysis of JACCRO GC-07, a randomized controlled trial. J Clin Oncol 37:1296–1304
Yoshikawa T, Terashima M, Mizusawa J et al (2019) Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol 4:208–216
Arai W, Hosoya Y, Hyodo M et al (2004) Alternate-day oral therapy with TS-1 for advanced gastric cancer. Int J Clin Oncol 9:143–148
Kimura Y, Kikkawa N, Iijima S et al (2003) A new regimen for S-1 therapy aiming at adverse reaction mitigation and prolonged medication by introducing a 1-week drug-free interval after each 2-week dosing session: Efficacy and feasibility in clinical practice. Gastric Cancer 6:34–39
Imamura H, Furukawa H, Kishimoto T et al (2007) Phase II study of 2-week S-1 administration followed by 1-week rest for gastric cancer. Hepatogastroenterology 54:2167–2171
Yamatsuji T, Fujiwara Y, Matsumoto H et al (2015) Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest. Mol Clin Oncol 3:527–532
Tsukuda M, Kida A, Fujii M et al (2005) Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer. Br J Cancer 93:884–889
Chirivella I, Bermejo B, Insa A et al (2009) Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat 114:479–484
Bosly A, Bron D, Hoof A et al (2008) Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP. Ann Hematol 87:277–283
Miyatani K, Saito H, Shimizu S et al (2019) Late start and insufficient S-1 dose in adjuvant chemotherapy can lead to poor prognosis in stage II/III gastric cancer. Int J Clin Oncol 24:1190–1196
Tatebe S, Tsujitani S, Nakamura S et al (2014) Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial. Gastric Cancer 17:508–513
Acknowledgements
This study was approved by T-CReDO (Tsukuba Clinical Research and Development Organization) (H29-320).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest that are directly relevant to the content of this manuscript.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Ogawa, K., Honda, M., Akashi, Y. et al. Comparison of 2- and 4-week S-1 administration as adjuvant chemotherapy for advanced gastric cancer. Int J Clin Oncol 25, 1807–1813 (2020). https://doi.org/10.1007/s10147-020-01719-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10147-020-01719-5