title: Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer.
abstract: OBJECTIVE
  The primary objective of this Phase I study was to assess the safety and tolerability of the vascular endothelial growth factor signalling inhibitor cediranib in combination with cisplatin plus an oral fluoropyrimidine, in Japanese patients with previously untreated advanced gastric cancer.
  
  
  METHODS
  Patients received continuous, once-daily oral doses of cediranib 20 mg in combination with either cisplatin (60 mg/m(2) iv day 1) plus S-1 (40-60 mg bid, days 1-21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80 mg/m(2) iv, day 1) plus capecitabine (1,000 mg/m(2) bid, days 1-14) every 3 weeks for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose-limiting toxicities (DLTs) was the first 21 days of cycle 1.
  
  
  RESULTS
  Fourteen patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all grade 3). Overall, the most common adverse events were decreased appetite, fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial responses that were ongoing at data cut-off.
  
  
  CONCLUSIONS
  Cediranib 20 mg/day in combination with cisplatin and S-1 or capecitabine was tolerable, with no new toxicities identified, and showed preliminary evidence of antitumour activity.
authors.affiliation: Kinki University School of Medicine, Osaka, Japan. taroh@cfs.med.osaka-u.ac.jp
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Keisei
authors.initials: K
authors.lastname: Taku
authors.forename: Takako Eguchi
authors.initials: TE
authors.lastname: Nakajima
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Shi
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Brown
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001066:Appetite / Q000187:drug effects; D019540:Area Under Curve; D044466:Asian People; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D007211:Indoles
chemical_list: D000069287:Capecitabine; D002945:Cisplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D010094:Oxonic Acid; D011799:Quinazolines; D005641:Tegafur; C500926:cediranib; D007211:Indoles