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Article

Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer

  • Authors:
    • Lin Yang
    • Yi Yang
    • Qiong Qin
    • Aiping Zhou
    • Jianjun Zhao
    • Jinwan Wang
    • Chang Shu
    • Xinghua Yuan
    • Songnian Hu
  • View Affiliations / Copyright

    Affiliations: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China
  • Pages: 93-98
    |
    Published online on: September 23, 2013
       https://doi.org/10.3892/mco.2013.191
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Abstract

Gastric cancer (GC) is the fourth most common type of cancer, accounting for an estimated one million new cases annually worldwide. locally advanced GC often recurs, even following curative surgical resection. Therefore, there is a need for an effective adjuvant chemotherapy regimen. The aim of this trial was to investigate the maximum tolerated dose (MTD) of S‑1 when administered in combination with oxaliplatin in postoperative GC patients. Oxaliplatin was administered at a fixed dose of 130 mg/m2 on day 1. S‑1 was administered from day 1 to 14 of a 3‑week cycle and escalated by 10 mg̸m2̸day from 60 to 80 mg/m2̸day. A total of 15 patients were enrolled in this study. No dose‑limiting toxicities (DLTs) occurred at level 1 (S‑1, 60 mg̸m2; n=3). One case of DLT (grade 3 vomiting) occurred at level 2 (S‑1, 70 mg/m2; n=6), whereas 2 cases of grade 3 vomiting were observed at level 3 (S‑1, 80 mg/m2; n=6). Based on these results, the MTD of S‑1 was initially determined to be 70 mg̸m2. Furthermore, we observed that cytochrome P450 2A6 (CYP2A6) 41349640C>G was associated with severe neutropenia (C/C vs. C/G vs. G/G = 0 vs. 33.33 vs. 100%; P=0.03297, Fisher's exact test) during the entire course of the treatment.
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1. 

Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar

2. 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

3. 

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 and Chua YJ; MAGIC Trial Participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 355:11–20. 2006. View Article : Google Scholar : PubMed/NCBI

4. 

Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM and Martenson JA: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 345:725–730. 2001. View Article : Google Scholar

5. 

Chollet P, Schöffski P, Weigang-Köhler K, Schellens JH, Cure H, Pavlidis N, Grünwald V, De Boer R, Wanders J and Fumoleau P; EORTC Early Clinical Studies Group: Phase II trial with S-1 in chemotherapy-naïve patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG). Eur J Cancer. 39:1264–1270. 2003.

6. 

Koizumi W, Kurihara M, Nakano S and Hasegawa K: Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 58:191–197. 2000. View Article : Google Scholar : PubMed/NCBI

7. 

Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y and Taguchi T: Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer. 34:1715–1720. 1998. View Article : Google Scholar : PubMed/NCBI

8. 

Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T and Ohashi Y: Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 29:4387–4393. 2011.

9. 

Koizumi W, Narahara H, Hara T, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 9:215–221. 2008. View Article : Google Scholar : PubMed/NCBI

10. 

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J and Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 358:36–46. 2008. View Article : Google Scholar : PubMed/NCBI

11. 

Higuchi K, Koizumi W, Yamada Y, et al: Randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin for first-line treatment of advanced gastric cancer. J Clin Oncol. 30(Suppl 34): abs. 60. 2012.

12. 

Li J, Yin J, Zhu X, Liu Y, Cao J, Lu F and Zuo Y: Phase I dose-escalating study of S-1 in combination with oxaliplatin for patients with advanced and/or metastatic colorectal cancer. Anticancer Drugs. 19:745–748. 2008. View Article : Google Scholar : PubMed/NCBI

13. 

Yamada Y, Tahara M, Miya T, Satoh T, Shirao K, Shimada Y, Ohtsu A, Sasaki Y and Tanigawara Y: Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer. Br J Cancer. 98:1034–1038. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Park I, Lee JL, Ryu MH, et al: Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer. Cancer Chemother Pharmacol. 65:473–480. 2010. View Article : Google Scholar : PubMed/NCBI

15. 

Kim GM, Jeung HC, Rha SY, Kim HS, Jung I, Nam BH, Lee KH and Chung HC: A randomized phase II trial of S-1-oxaliplatin versus capecitabine-oxaliplatin in advanced gastric cancer. Eur J Cancer. 48:518–526. 2012. View Article : Google Scholar : PubMed/NCBI

16. 

Kodera Y, Ito S, Mochizuki Y, et al: Chubu Clinical Oncology Group: A phase II study of radical surgery followed by postoperative chemotherapy with S-1 for gastric carcinoma with free cancer cells in the peritoneal cavity (CCOG0301 study). Eur J Surg Oncol. 35:1158–1163. 2009. View Article : Google Scholar

17. 

Liu B, Ying J, Luo C, Xu Q, Zhu L and Zhong H: S-1 combined with oxaliplatin as first line chemotherapy for Chinese advanced gastric cancer patients. Hepatogastroenterology. 59:649–653. 2012.PubMed/NCBI

18. 

Yoshikawa T, Omura K, Kobayashi O, Nashimoto A, Takabayashi A, Yamada T, Yamaue H, Fujii M, Yamaguchi T and Nakajima T: A phase II study of preoperative chemotherapy with S-1 plus cisplatin followed by D2/D3 gastrectomy for clinically serosa-positive gastric cancer (JACCRO GC-01 study). Eur J Surg Oncol. 36:546–551. 2010. View Article : Google Scholar : PubMed/NCBI

19. 

El Sayed YM and Sadee W: Metabolic activation of ftorafur [R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil]: the microsomal oxidative pathway. Biochem Pharmacol. 31:3006–3008. 1982.

20. 

Ikeda K, Yoshisue K, Matsushima E, Nagayama S, Kobayashi K, Tyson CA, Chiba K and Kawaguchi Y: Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro. Clin Cancer Res. 6:4409–4415. 2000.PubMed/NCBI

21. 

Fujita K, Yamamoto W, Endo S, et al: CYP2A6 and the plasma level of 5-chloro-2,4-dihydroxypyridine are determinants of the pharmacokinetic variability of tegafur and 5-fluorouracil, respectively, in Japanese patients with cancer given S-1. Cancer Sci. 99:1049–1054. 2008. View Article : Google Scholar

22. 

Kim KP, Jang G, Hong YS, et al: Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity. Br J Cancer. 104:605–612. 2011. View Article : Google Scholar : PubMed/NCBI

23. 

Ariyoshi N, Sawamura Y and Kamataki T: A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun. 281:810–814. 2001. View Article : Google Scholar : PubMed/NCBI

24. 

Xu C, Rao YS, Xu B, Hoffmann E, Jones J, Sellers EM and Tyndale RF: An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles. Biochem Biophys Res Commun. 290:318–324. 2002.PubMed/NCBI

25. 

Yoshida R, Nakajima M, Watanabe Y, Kwon JT and Yokoi T: Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Br J Clin Pharmacol. 54:511–517. 2002. View Article : Google Scholar : PubMed/NCBI

26. 

Kim WY, Nakata B and Hirakawa K: Alternative pharmacokinetics of S-1 components, 5-fluorouracil, dihydrofluorouracil and alpha-fluoro-beta-alanine after oral administration of S-1 following total gastrectomy. Cancer Sci. 98:1604–1608. 2007. View Article : Google Scholar

27. 

Kochi M, Fujii M, Kanamori N, Kaiga T, Aizaki K, Takahashi T and Takayama T: Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients. Cancer Chemother Pharmacol. 60:693–701. 2007. View Article : Google Scholar : PubMed/NCBI

28. 

Kong SY, Lim HS, Nam BH, et al: Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes in metastatic gastric cancer. Pharmacogenomics. 10:1147–1155. 2009. View Article : Google Scholar : PubMed/NCBI

29. 

Park SR, Kong SY, Nam BH, et al: CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients. Br J Cancer. 104:1126–1134. 2011. View Article : Google Scholar : PubMed/NCBI

30. 

Christian K, Lang M, Maurel P and Raffalli-Mathieu F: Interaction of heterogeneous nuclear ribonucleoprotein A1 with cytochrome P450 2A6 mRNA: implications for post-transcriptional regulation of the CYP2A6 gene. Mol Pharmacol. 65:1405–1414. 2004. View Article : Google Scholar : PubMed/NCBI

31. 

Raffalli-Mathieu F, Glisovic T, Ben-David Y and Lang MA: Heterogeneous nuclear ribonucleoprotein A1 and regulation of the xenobiotic-inducible gene Cyp2a5. Mol Pharmacol. 61:795–799. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang L, Yang Y, Qin Q, Zhou A, Zhao J, Wang J, Shu C, Yuan X and Hu S: Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer. Mol Clin Oncol 2: 93-98, 2014.
APA
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J. ... Hu, S. (2014). Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer. Molecular and Clinical Oncology, 2, 93-98. https://doi.org/10.3892/mco.2013.191
MLA
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J., Shu, C., Yuan, X., Hu, S."Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer". Molecular and Clinical Oncology 2.1 (2014): 93-98.
Chicago
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J., Shu, C., Yuan, X., Hu, S."Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer". Molecular and Clinical Oncology 2, no. 1 (2014): 93-98. https://doi.org/10.3892/mco.2013.191
Copy and paste a formatted citation
x
Spandidos Publications style
Yang L, Yang Y, Qin Q, Zhou A, Zhao J, Wang J, Shu C, Yuan X and Hu S: Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer. Mol Clin Oncol 2: 93-98, 2014.
APA
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J. ... Hu, S. (2014). Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer. Molecular and Clinical Oncology, 2, 93-98. https://doi.org/10.3892/mco.2013.191
MLA
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J., Shu, C., Yuan, X., Hu, S."Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer". Molecular and Clinical Oncology 2.1 (2014): 93-98.
Chicago
Yang, L., Yang, Y., Qin, Q., Zhou, A., Zhao, J., Wang, J., Shu, C., Yuan, X., Hu, S."Dose‑finding study on adjuvant chemotherapy with S‑1 plus oxaliplatin for gastric cancer". Molecular and Clinical Oncology 2, no. 1 (2014): 93-98. https://doi.org/10.3892/mco.2013.191
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