PMID- 23829943
OWN - NLM
STAT- MEDLINE
DCOM- 20140505
LR  - 20211021
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 6
DP  - 2013 Jul 8
TI  - A phase I study of ridaforolimus in adult Chinese patients with advanced solid 
      tumors.
PG  - 48
LID - 10.1186/1756-8722-6-48 [doi]
AB  - PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
FAU - Liu, Lian
AU  - Liu L
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Zhang, Wen
AU  - Zhang W
FAU - Li, Wenhua
AU  - Li W
FAU - Lv, Fangfang
AU  - Lv F
FAU - Xia, Zuguang
AU  - Xia Z
FAU - Zhang, Sheng
AU  - Zhang S
FAU - Liu, Wen
AU  - Liu W
FAU - Zandvliet, Anthe S
AU  - Zandvliet AS
FAU - Waajen, Sylvia
AU  - Waajen S
FAU - Zhang, Li Xin
AU  - Zhang LX
FAU - Yan, Li
AU  - Yan L
FAU - Li, Jin
AU  - Li J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20130708
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 48Z35KB15K (ridaforolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Sirolimus/adverse effects/*analogs & derivatives/pharmacokinetics/therapeutic use
PMC - PMC3716995
EDAT- 2013/07/09 06:00
MHDA- 2014/05/06 06:00
PMCR- 2013/07/08
CRDT- 2013/07/09 06:00
PHST- 2013/06/21 00:00 [received]
PHST- 2013/07/04 00:00 [accepted]
PHST- 2013/07/09 06:00 [entrez]
PHST- 2013/07/09 06:00 [pubmed]
PHST- 2014/05/06 06:00 [medline]
PHST- 2013/07/08 00:00 [pmc-release]
AID - 1756-8722-6-48 [pii]
AID - 10.1186/1756-8722-6-48 [doi]
PST - epublish
SO  - J Hematol Oncol. 2013 Jul 8;6:48. doi: 10.1186/1756-8722-6-48.