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.
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.
Yamamoto
Noboru
N
Division of Internal Medicine, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. nbryamam@ncc.go.jp
Tamura
Tomohide
T
Yamamoto
Nobuyuki
N
Yamada
Kazuhiko
K
Yamada
Yasuhide
Y
Nokihara
Hiroshi
H
Fujiwara
Yutaka
Y
Takahashi
Toshiaki
T
Murakami
Haruyasu
H
Boku
Narikazu
N
Yamazaki
Kentaro
K
Puchalski
Thomas A
TA
Shin
Eisei
E
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
D020533:Angiogenesis Inhibitors; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D007211:Indoles