title: Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  To evaluate safety and tolerability of cediranib, a highly potent and selective vascular endothelial growth factor signaling inhibitor, in Japanese patients with advanced solid tumors refractory to standard therapies.
  
  
  METHODS
  In part A (n = 16), patients received once-daily oral cediranib (10-45 mg) to identify the maximum tolerated dose (MTD). In part B (n = 24), patients with non-small-cell lung cancer or colorectal cancer received multiple daily doses at the MTD.
  
  
  RESULTS
  Cediranib 30 mg/day was considered the MTD since 50% of evaluable patients receiving 45 mg/day experienced dose-limiting toxicities in part A (proteinuria and diarrhea n = 1, proteinuria n = 1, thrombocytopenia n = 1). The most common adverse events were diarrhea (n = 34) and hypertension (n = 32). Pharmacokinetic analysis confirmed cediranib as suitable for once-daily oral dosing. Of 32 evaluable patients, two had partial RECIST responses and 24 had stable disease > or =8 weeks.
  
  
  CONCLUSIONS
  Cediranib was generally well tolerated at < or =30 mg/day in these Japanese patients and showed encouraging antitumor activity.
authors.affiliation: Division of Internal Medicine, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. nbryamam@ncc.go.jp
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Puchalski
authors.forename: Eisei
authors.initials: E
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D007211:Indoles