PMID- 23406528
OWN - NLM
STAT- MEDLINE
DCOM- 20130812
LR  - 20211203
IS  - 1744-7666 (Electronic)
IS  - 1465-6566 (Linking)
VI  - 14
IP  - 4
DP  - 2013 Mar
TI  - Everolimus in colorectal cancer.
PG  - 505-13
LID - 10.1517/14656566.2013.770473 [doi]
AB  - INTRODUCTION: There has been a strong preclinical rationale for studying 
      mammalian target of rapamycin (mTOR) inhibitors as single agents or in 
      combination, in multiple malignancies and colorectal cancer in particular. AREAS 
      COVERED: The authors summarize the complete clinical experience to date of all 
      trials, both published and in abstract form, of everolimus in colorectal cancer. 
      While initial Phase I trials showed promise, further studies have confirmed that 
      single agent everolimus is not active in advanced metastatic colorectal carcinoma 
      with trials showing single agent tolerability, but without significant hints of 
      efficacy in terms of either objective tumor responses or prolonged stable 
      disease. Combination regimens, including combinations with cytotoxic 
      chemotherapy, and inhibitors of VEGF, EGFR and HDAC have been tested specifically 
      in the colorectal setting in Phase I and Phase II clinical trials. The authors 
      discuss the potential reasons for mixed results and suggest future directions for 
      the development of everolimus in colorectal malignancies. EXPERT OPINION: Studies 
      demonstrate limited clinical activity of everolimus for the treatment of advanced 
      colorectal cancer and have been complicated by increases in toxicity. However, 
      the central role of the PI3K/mTOR pathway in cancer biology suggests that other 
      drug combinations with mTOR inhibition may still merit evaluation.
FAU - Altomare, Ivy
AU  - Altomare I
AD  - Duke University Medical Center, Division of Medical Oncology, 3100 Tower Blvd Ste 
      600, Durham, NC 27707, USA. Ivy.altomare@duke.edu
FAU - Hurwitz, Herbert
AU  - Hurwitz H
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130213
PL  - England
TA  - Expert Opin Pharmacother
JT  - Expert opinion on pharmacotherapy
JID - 100897346
RN  - 9HW64Q8G6G (Everolimus)
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  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Colorectal Neoplasms/*drug therapy/metabolism/pathology
MH  - Disease-Free Survival
MH  - Drug Screening Assays, Antitumor
MH  - Everolimus
MH  - Humans
MH  - Molecular Structure
MH  - Sirolimus/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
EDAT- 2013/02/15 06:00
MHDA- 2013/08/13 06:00
CRDT- 2013/02/15 06:00
PHST- 2013/02/15 06:00 [entrez]
PHST- 2013/02/15 06:00 [pubmed]
PHST- 2013/08/13 06:00 [medline]
AID - 10.1517/14656566.2013.770473 [doi]
PST - ppublish
SO  - Expert Opin Pharmacother. 2013 Mar;14(4):505-13. doi: 
      10.1517/14656566.2013.770473. Epub 2013 Feb 13.