PMID- 26507507
OWN - NLM
STAT- MEDLINE
DCOM- 20161018
LR  - 20161230
IS  - 1938-0666 (Electronic)
IS  - 1526-8209 (Linking)
VI  - 16
IP  - 1
DP  - 2016 Feb
TI  - Dosing and Safety Implications for Oncologists When Administering Everolimus to 
      Patients With Hormone Receptor-Positive Breast Cancer.
PG  - 18-22
LID - S1526-8209(15)00215-3 [pii]
LID - 10.1016/j.clbc.2015.09.004 [doi]
AB  - Aberrations in the phosphoinositide 3-kinase/protein kinase B/mammalian target of 
      rapamycin pathway are common abnormalities in breast cancer and are associated 
      with the development of resistance to endocrine- and human epidermal growth 
      factor receptor (HER)2-targeted therapies. Because of the significant improvement 
      in progression-free survival for everolimus plus exemestane compared with 
      exemestane plus placebo, everolimus, an mTOR inhibitor, was approved in the 
      United States for the treatment of patients with hormone receptor-positive (HR+), 
      HER-negative, advanced breast cancer whose disease had progressed while receiving 
      letrozole or anastrozole. To provide optimal prevention and management 
      strategies, it is crucial that clinicians are aware of the adverse events (AEs) 
      associated with mTOR inhibition. Understanding the appropriate dose modifications 
      will help reduce toxicity and improve drug tolerance, thus achieving the optimal 
      benefit from everolimus. Analyses of data from the Breast Cancer Trials of Oral 
      Everolimus 2 trial have shown that, despite a greater frequency of AEs in the 
      everolimus plus exemestane treatment arm, the AEs were effectively managed with 
      temporary dose reductions or interruptions. In some cases, the full dose of 
      everolimus could be resumed. Despite a lower mean dose and duration of exposure 
      in patients aged >/= 70 versus < 70 years, everolimus plus exemestane was similarly 
      efficacious, suggesting that appropriate dose reductions for toxicity will not 
      adversely impact efficacy. Appropriate modification of the everolimus dose and 
      dose delay according to the severity of AEs, with resumption of the optimal dose 
      of everolimus when toxicity has improved, will positively affect patient outcomes 
      in HR+ advanced breast cancer.
CI  - Copyright (c) 2016 The Author. Published by Elsevier Inc. All rights reserved.
FAU - Rugo, Hope S
AU  - Rugo HS
AD  - University of California, San Francisco, Helen Diller Family Comprehensive Cancer 
      Center, San Francisco, CA. Electronic address: hope.rugo@ucsf.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150929
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage/*adverse effects
MH  - Breast Neoplasms/*drug therapy
MH  - Everolimus/*administration & dosage/*adverse effects
MH  - Female
MH  - Humans
MH  - Medical Oncology/*methods
MH  - Receptor, ErbB-2/biosynthesis
MH  - Receptors, Estrogen/biosynthesis
MH  - Receptors, Progesterone/biosynthesis
OTO - NOTNLM
OT  - Exemestane
OT  - Hormone receptor positive advanced breast cancer
OT  - Pneumonitis
OT  - Stomatitis
OT  - mTOR inhibition
EDAT- 2015/10/29 06:00
MHDA- 2016/10/19 06:00
CRDT- 2015/10/29 06:00
PHST- 2015/06/16 00:00 [received]
PHST- 2015/09/11 00:00 [accepted]
PHST- 2015/10/29 06:00 [entrez]
PHST- 2015/10/29 06:00 [pubmed]
PHST- 2016/10/19 06:00 [medline]
AID - S1526-8209(15)00215-3 [pii]
AID - 10.1016/j.clbc.2015.09.004 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2016 Feb;16(1):18-22. doi: 10.1016/j.clbc.2015.09.004. Epub 
      2015 Sep 29.