PMID- 21177421
OWN - NLM
STAT- MEDLINE
DCOM- 20110519
LR  - 20211203
IS  - 1542-6270 (Electronic)
IS  - 1060-0280 (Linking)
VI  - 45
IP  - 1
DP  - 2011 Jan
TI  - Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of 
      advanced renal cell carcinoma.
PG  - 78-83
LID - 10.1345/aph.1M288 [doi]
AB  - OBJECTIVE: To review clinical trials and main characteristics of everolimus, with 
      focus on treatment of advanced renal cell carcinoma. DATA SOURCES: Pertinent data 
      were identified primarily through a search of MEDLINE and PubMed (1966-November 
      2010) using the primary search terms everolimus, RAD001, renal cell carcinoma, 
      and mTOR inhibitors. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the 
      safety and efficacy of everolimus in patients with cancer were evaluated, 
      including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies 
      evaluating use of everolimus in patients with renal cell carcinoma. DATA 
      SYNTHESIS: Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor 
      approved for the management of patients with advanced renal cell carcinoma who 
      progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the 
      mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well 
      as decreased angiogenesis. A usual starting dose for patients with renal cell 
      carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism, 
      primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions 
      with inducers and inhibitors of this enzyme. Most commonly reported adverse 
      events associated with everolimus include anemia, hyperglycemia, 
      hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was 
      based on the results of a Phase 3 trial that demonstrated an increase in median 
      progression-free survival by 2.1 months in patients receiving everolimus therapy 
      as compared to placebo. The drug was recently added to the National Comprehensive 
      Cancer Network guidelines as a treatment option for patients with advanced renal 
      cell carcinoma who have progressed on tyrosine kinase therapy. CONCLUSIONS: Based 
      on a review of the currently available literature, everolimus provides a safe and 
      efficacious treatment option for patients with renal cell carcinoma who have 
      progressed on treatment with sunitinib and/or sorafenib.
FAU - Grgic, Tatjana
AU  - Grgic T
AD  - Department of Pharmacy, Duke University Medical Center, Durham, NC, USA. 
      tatjana.grgic@duke.edu
FAU - Mis, Lydia
AU  - Mis L
FAU - Hammond, Julia M
AU  - Hammond JM
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20101221
PL  - United States
TA  - Ann Pharmacother
JT  - The Annals of pharmacotherapy
JID - 9203131
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Carcinoma, Renal Cell/*drug therapy/metabolism
MH  - Drug Costs
MH  - Drug Interactions
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects/economics/pharmacology/*therapeutic use
MH  - Kidney Neoplasms/*drug therapy/metabolism
MH  - Sirolimus/adverse effects/*analogs & 
      derivatives/economics/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2010/12/24 06:00
MHDA- 2011/05/20 06:00
CRDT- 2010/12/24 06:00
PHST- 2010/12/24 06:00 [entrez]
PHST- 2010/12/24 06:00 [pubmed]
PHST- 2011/05/20 06:00 [medline]
AID - aph.1M288 [pii]
AID - 10.1345/aph.1M288 [doi]
PST - ppublish
SO  - Ann Pharmacother. 2011 Jan;45(1):78-83. doi: 10.1345/aph.1M288. Epub 2010 Dec 21.