title: Phase I study for ridaforolimus, an oral mTOR inhibitor, in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  Ridaforolimus is a non-prodrug mTOR inhibitor. The safety, pharmacokinetics (PK), and antitumor activity of oral ridaforolimus were assessed in Japanese patients with refractory solid tumors.
  
  
  METHODS
  Ridaforolimus (20 or 40 mg) was administered as a single dose on Day 1, followed by once daily dosing five times a week for a 3-week cycle beginning on Day 8. Full PK sampling was performed on Days 1 and 26.
  
  
  RESULTS
  Thirteen patients (7 at 20 mg and 6 at 40 mg) were enrolled. The median treatment duration was 82 days. The most common drug-related adverse events were stomatitis, hypertriglyceridemia, and proteinuria. Two patients had dose-limiting toxicities (grade 3 stomatitis at 20 mg, and grade 3 anorexia and vomiting at 40 mg). Four patients had grade 1 interstitial pneumonitis. Ridaforolimus in the whole blood was rapidly absorbed and slowly eliminated with a half-life of approximately 56-58 h after a single dose. Two patients (with non-small cell lung cancer and angiosarcoma, respectively) achieved a partial response, and five patients (one with thymic cancer and four with soft tissue sarcomas) had a stable disease for ≥ 16 weeks.
  
  
  CONCLUSIONS
  Ridaforolimus was well tolerated up to a dose of 40 mg in Japanese patients. Preliminary evidence of antitumor activity was observed for patients with solid tumors. Further investigation at this dose is warranted.
authors.affiliation: Division of Internal Medicine, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Seki
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Goto
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibata
authors.forename: Maki
authors.initials: M
authors.lastname: Tanioka
authors.forename: Hajime
authors.initials: H
authors.lastname: Asahina
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Noguchi
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; C515074:ridaforolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus