title: Phase I study of two schedules of oral S-1 in combination with fixed doses of oxaliplatin and bevacizumab in patients with advanced solid tumors.
abstract: BACKGROUND
  S-1 is a novel oral agent combining the 5-fluorouracil (FU) prodrug tegafur with gimeracil and oteracil, which inhibit 5-FU degradation by dihydropyrimidine dehydrogenase and phosphorylation within the gastrointestinal tract, respectively. The study was designed to identify the maximum tolerable dose and the dose-limiting toxicities of two schedules of S-1 combined with oxaliplatin and bevacizumab, in advanced solid tumor patients.
  
  
  METHODS
  Schedule A: S-1 was administered orally at 20 mg/m(2) twice daily for 14 consecutive days, escalated by 5 mg/m(2), with fixed-dose intravenous bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) on day 1 of each 3-week cycle. Schedule B: S-1 was administered at 25 mg/m(2) twice daily for 7 consecutive days, escalated by 5 mg/m(2), with fixed-dose intravenous bevacizumab 5 mg/kg and oxaliplatin 85 mg/m(2) on day 1 of each 2-week cycle.
  
  
  RESULTS
  The maximum tolerated dose and recommended phase II dose of S-1 was 25 mg/m(2) twice daily for 14 days for schedule A and 35 mg/m(2) twice daily for 7 days for schedule B. The most common dose-limiting toxicities were grade 3 diarrhea. Both regimens were well tolerated. No pharmacokinetic interactions between oxaliplatin and S-1 components were observed.
  
  
  CONCLUSIONS
  S-1, oxaliplatin and bevacizumab can be administered with acceptable safety and tolerability and without evidence of pharmacokinetic interactions.
authors.affiliation: Cancer Centers of the Carolinas, Spartanburg, SC 29307, USA. ki.chung@usoncology.com
authors.forename: Ki Y
authors.initials: KY
authors.lastname: Chung
authors.forename: Kaku
authors.initials: K
authors.lastname: Saito
authors.forename: Christopher
authors.initials: C
authors.lastname: Zergebel
authors.forename: Ellen
authors.initials: E
authors.lastname: Hollywood
authors.forename: Michal
authors.initials: M
authors.lastname: Segal
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid