title: Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.
abstract: BACKGROUND
  Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients.
  
  
  METHODS
  Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival.
  
  
  RESULTS
  A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates.
  
  
  CONCLUSIONS
  Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy.
  
  
  BACKGROUND
  NCT01918852.
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: J J M
authors.initials: JJM
authors.lastname: Kwakman
authors.affiliation: Department of Medical Oncology, Maxima Medical Center, Eindhoven.
authors.forename: L H J
authors.initials: LHJ
authors.lastname: Simkens
authors.affiliation: Department of Medical Oncology, Martini Hospital, Groningen.
authors.forename: J M
authors.initials: JM
authors.lastname: van Rooijen
authors.affiliation: Department of Medical Oncology, VieCuri Medical Center, Venlo.
authors.forename: A J
authors.initials: AJ
authors.lastname: van de Wouw
authors.affiliation: Department of Medical Oncology, Amphia Hospital, Breda.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ten Tije
authors.affiliation: Department of Medical Oncology, Catharina Hospital, Eindhoven.
authors.forename: G J M
authors.initials: GJM
authors.lastname: Creemers
authors.affiliation: Department of Medical Oncology, Northwest Clinics, Alkmaar.
authors.forename: M P
authors.initials: MP
authors.lastname: Hendriks
authors.affiliation: Department of Medical Oncology, Sint Antonius Hospital, Nieuwegein.
authors.forename: M
authors.initials: M
authors.lastname: Los
authors.affiliation: Department of Medical Oncology, TweeSteden Hospital, Tilburg.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Alphen
authors.affiliation: Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden.
authors.forename: M B
authors.initials: MB
authors.lastname: Polée
authors.affiliation: Department of Medical Oncology, Slingeland Hospital, Doetinchem.
authors.forename: E W
authors.initials: EW
authors.lastname: Muller
authors.affiliation: Department of Medical Oncology, Tergooi Hospital, Hilversum.
authors.forename: A M T
authors.initials: AMT
authors.lastname: van der Velden
authors.affiliation: Department of Medical Oncology, Rijnstate Hospital, Arnhem.
authors.forename: T
authors.initials: T
authors.lastname: van Voorthuizen
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, University Utrecht, Utrecht.
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Clinical Trial Department, Netherlands Comprehensive Cancer Organisation (IKNL), Nijmegen.
authors.forename: L
authors.initials: L
authors.lastname: Mol
authors.affiliation: Department of Biometrics, The Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van Werkhoven
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: C J A
authors.initials: CJA
authors.lastname: Punt
mesh_terms: D000368:Aged; D000069287:Capecitabine / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D010094:Oxonic Acid / Q000627:therapeutic use*; D005641:Tegafur / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000069287:Capecitabine
keywords: S-1; capecitabine; hand–foot syndrome; metastatic colorectal cancer