title: Randomised phase II study of S-1/cisplatin plus TSU-68 vs S-1/cisplatin in patients with advanced gastric cancer.
abstract: BACKGROUND
  This study aimed to determine whether combination S-1 plus cisplatin (CDDP) therapy, the most widely used therapy for Japanese patients with advanced gastric cancer, and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment.
  
  
  METHODS
  Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were randomised into two groups: TSU-68 plus S-1/CDDP (group A) and S-1/CDDP (group B) groups. Both patient groups received identical S-1 and CDDP dosages. TSU-68 was orally administered for 35 consecutive days. Group B patients received S-1 orally twice daily for three consecutive weeks, followed by intravenous CDDP on day 8. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  Median PFS periods were 208 and 213 days in groups A and B, respectively (P=0.427). Median survival periods for groups A and B were 497.0 and 463.5 days, respectively (P=0.219). No statistically significant differences were noted for PFS, survival or the adverse event (AE) incidence rate. All AEs were expected according to previous reports for TSU-68, TS-1, and CDDP.
  
  
  CONCLUSIONS
  Combination therapy involving TSU-68, S-1, and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers. However, factors related to therapeutic efficacy should be investigated further.
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, Sagamihara 228-8520, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Koizumi
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Hosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Takinishi
authors.forename: N
authors.initials: N
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Muro
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Nishina
authors.forename: N
authors.initials: N
authors.lastname: Fuse
authors.forename: T
authors.initials: T
authors.lastname: Esaki
authors.forename: M
authors.initials: M
authors.lastname: Takagi
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D000078183:Oxindoles; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011422:Propionates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011758:Pyrroles; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C412603:orantinib; D002945:Cisplatin
references.citation: Lancet. 2010 Aug 28;376(9742):687-97
references.pmid: 20728210
references.citation: J Clin Oncol. 2005 Oct 1;23(28):7199-206
references.pmid: 16192604
references.citation: Cancer Res. 2000 Aug 1;60(15):4152-60
references.pmid: 10945623
references.citation: Ann Intern Med. 1980 Oct;93(4):533-6
references.pmid: 7436184
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: J Thorac Oncol. 2012 Feb;7(2):427-33
references.pmid: 22071785
references.citation: Gut Liver. 2009 Jun;3(2):88-94
references.pmid: 20431729
references.citation: Cancer Chemother Pharmacol. 2011 Feb;67(2):315-24
references.pmid: 20390419
references.citation: Cancer Chemother Pharmacol. 2011 May;67(5):1101-9
references.pmid: 20676675
references.citation: Eur J Cancer. 2013 Sep;49(13):2832-40
references.pmid: 23764238
references.citation: J Clin Oncol. 2003 Jan 1;21(1):54-9
references.pmid: 12506170
references.citation: Lancet Oncol. 2009 Nov;10(11):1063-9
references.pmid: 19818685
references.citation: Cancer Chemother Pharmacol. 2011 May;67(5):1119-28
references.pmid: 20676674
references.citation: Breast Cancer. 2014 Jan;21(1):20-7
references.pmid: 22382811
references.citation: Invest New Drugs. 2012 Aug;30(4):1501-10
references.pmid: 21567184
references.citation: Drug Metab Dispos. 2008 Jun;36(6):1003-9
references.pmid: 18322074
references.citation: Drug Metab Dispos. 2000 Dec;28(12):1457-63
references.pmid: 11095583
references.citation: J Clin Oncol. 2011 Oct 20;29(30):3968-76
references.pmid: 21844504
references.citation: Lancet Oncol. 2008 Mar;9(3):215-21
references.pmid: 18282805