PMID- 23921574
OWN - NLM
STAT- MEDLINE
DCOM- 20140428
LR  - 20211203
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 72
IP  - 4
DP  - 2013 Oct
TI  - Tolerability, safety and pharmacokinetics of ridaforolimus in combination with 
      bicalutamide in patients with asymptomatic, metastatic castration-resistant 
      prostate cancer (CRPC).
PG  - 909-16
LID - 10.1007/s00280-013-2250-6 [doi]
AB  - PURPOSE: Recent data indicate that there is a significant cross-talk between the 
      PI3K/Akt/mTOR and androgen receptor signaling pathways. We evaluated safety and 
      tolerability as well as potential drug-drug interaction of ridaforolimus, a 
      mammalian target of rapamycin (mTOR) inhibitor, when combined with the androgen 
      receptor inhibitor bicalutamide in patients with asymptomatic, metastatic 
      castration-resistant prostate cancer. PATIENTS AND METHODS: Patients were treated 
      with the combination of ridaforolimus 30 mg/day for 5 consecutive days each week 
      and bicalutamide 50 mg/day. Ridaforolimus pharmacokinetics was assessed with and 
      without bicalutamide. RESULTS: Twelve patients were enrolled including 1 screen 
      failure. Dose reductions were required in 7 patients. Three of the 11 patients 
      experienced a dose-limited toxicity, 1 with Grade 3 hyperglycemia and 2 with 
      Grade 2 stomatitis leading to <75 % of planned ridaforolimus dose during the 
      first 35 days of study treatment. The pharmacokinetic results showed no 
      differences in exposures to ridaforolimus with and without concomitant 
      bicalutamide administration. CONCLUSIONS: Although there was no evidence of a 
      clinically relevant pharmacological drug-drug interaction, the occurrence of 
      dose-limiting toxicities in 3 of 11 evaluable patients at a reduced dose of 
      ridaforolimus of 30 mg/day suggests that this combination may not be well suited 
      for asymptomatic or minimally symptomatic prostate cancer patients.
FAU - Meulenbeld, Hielke J
AU  - Meulenbeld HJ
AD  - Department of Medical Oncology, Erasmus University Medical Center, Daniel den 
      Hoed Cancer Center, Groene Hilledijk 301, 3008 AE, Rotterdam, The Netherlands, 
      hielkem@hotmail.com.
FAU - de Bono, Johann S
AU  - de Bono JS
FAU - Tagawa, Scott T
AU  - Tagawa ST
FAU - Whang, Young E
AU  - Whang YE
FAU - Li, Xiaoyun
AU  - Li X
FAU - Heath, Karl H
AU  - Heath KH
FAU - Zandvliet, Anthe S
AU  - Zandvliet AS
FAU - Ebbinghaus, Scot W
AU  - Ebbinghaus SW
FAU - Hudes, Gary R
AU  - Hudes GR
FAU - de Wit, Ronald
AU  - de Wit R
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130807
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Androgen Antagonists)
RN  - 0 (Anilides)
RN  - 0 (Nitriles)
RN  - 0 (Tosyl Compounds)
RN  - 48Z35KB15K (ridaforolimus)
RN  - A0Z3NAU9DP (bicalutamide)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aged
MH  - Androgen Antagonists/adverse effects/pharmacokinetics/therapeutic use
MH  - Anilides/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Nitriles/administration & dosage
MH  - Orchiectomy
MH  - Prospective Studies
MH  - Prostatic Neoplasms/*drug therapy/pathology
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tosyl Compounds/administration & dosage
EDAT- 2013/08/08 06:00
MHDA- 2014/04/29 06:00
CRDT- 2013/08/08 06:00
PHST- 2013/03/28 00:00 [received]
PHST- 2013/07/26 00:00 [accepted]
PHST- 2013/08/08 06:00 [entrez]
PHST- 2013/08/08 06:00 [pubmed]
PHST- 2014/04/29 06:00 [medline]
AID - 10.1007/s00280-013-2250-6 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2013 Oct;72(4):909-16. doi: 
      10.1007/s00280-013-2250-6. Epub 2013 Aug 7.