title: A phase I study of ridaforolimus in adult Chinese patients with advanced solid tumors.
abstract: OBJECTIVE
  Ridaforolimus (AP23573, MK-8669 or deforolimus) is an inhibitor of mammalian target of rapamycin (mTOR), an important regulator in the cell survival pathway. This open-label, single center phase I study aimed to investigate the pharmacokinetic (PK) and safety profiles of ridaforolimus in Chinese patients with treatment-refractory advanced or relapsed solid tumors. The PK data generated from these Chinese patients were further compared with those previously reported in Caucasian and Japanese patient populations.
  
  
  METHODS
  The patients were given an oral dose of 40 mg of ridaforolimus on Day 1 of the study. On Day 8, patients were initiated on a treatment regimen that comprised a once daily dose of 40 mg of ridaforolimus for five consecutive days, followed by a 2-day off-drug interval. Patients repeated this regimen until disease progression or intolerance. Blood samples were collected at specific times pre- and post-treatment to establish the PK profile of ridaforolimus in all patients.
  
  
  RESULTS
  Fifteen patients were given at least one dose of 40 mg of ridaforolimus. The median absorption lag-time was 2 hours, the median Tmax was 4 hours and the mean elimination half-life was 53 hours. The accumulation ratio for AUC(0-24hr) was 1.3 on day 19 (steady state)/day 1 (after a single dose). The most common drug-related adverse events (AEs) that occurred in ≥40% of patients were stomatitis, proteinuria, leukopenia, hyperglycemia, and pyrexia. Grade 3/4 drug-related AEs were anemia, stomatitis, fatigue, thrombocytopenia, constipation, gamma glutamyltransferase increase, and proteinuria. All 11 evaluable patients achieved stable disease.
  
  
  CONCLUSIONS
  Oral ridaforolimus at a daily dose of 40 mg were generally well tolerated in Chinese patients with advanced or refractory solid tumors. Adverse events and PK profiles of ridaforolimus in this study were similar to those from Caucasian and Japanese patients reported previously.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lv
authors.forename: Zuguang
authors.initials: Z
authors.lastname: Xia
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Anthe S
authors.initials: AS
authors.lastname: Zandvliet
authors.forename: Sylvia
authors.initials: S
authors.lastname: Waajen
authors.forename: Li Xin
authors.initials: LX
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C515074:ridaforolimus; D020123:Sirolimus