PMID- 25199576
OWN - NLM
STAT- MEDLINE
DCOM- 20151001
LR  - 20181202
IS  - 1938-0666 (Electronic)
IS  - 1526-8209 (Linking)
VI  - 15
IP  - 1
DP  - 2015 Feb
TI  - Everolimus-induced hematologic changes in patients with metastatic breast cancer.
PG  - 48-53
LID - S1526-8209(14)00155-4 [pii]
LID - 10.1016/j.clbc.2014.07.002 [doi]
AB  - BACKGROUND: Everolimus, which inhibits the mammalian target of rapamycin (mTOR), 
      is increasingly used in breast cancer and familiarity with its full range of 
      toxicity is critical for practicing oncologists. PATIENTS AND METHODS: We studied 
      hematologic changes in 31 patients with metastatic breast cancer treated in a 
      phase II clinical trial using everolimus. Complete blood counts were collected at 
      baseline, 2 weeks, 4 weeks, every 4 weeks during treatment, and 1 month after 
      discontinuation. Adverse events were defined using Common Toxicity Criteria 
      version 3. Linear mixed models with fixed effects of time and random intercepts 
      and slopes were used to study trends and comparisons were conducted using paired 
      t tests. RESULTS: Anemia was reported in 22 patients (71%), thrombocytopenia in 
      17 (55%), and leukopenia in 14 (45%). These were predominantly grade 1 or 2 and 
      did not require dose modification. Red blood cell mean corpuscular volume (MCV) 
      and mean corpuscular hemoglobin (MCH) both decreased significantly over time (P < 
      .0001) starting at 2 weeks with no significant change in mean corpuscular 
      hemoglobin concentration (MCHC) (P = .104). Both MCV and MCH increased 1 month 
      after treatment discontinuation (P values < .0001 and .0003, respectively) 
      indicating reversibility of this effect. Although total leukocyte counts remained 
      largely stable, lymphocyte percentage progressively decreased over time with a 
      trend for increased neutrophils. CONCLUSION: In addition to anemia, leukopenia, 
      and thrombocytopenia, everolimus consistently induces red cell microcytosis and 
      reduced hemoglobin content. Lymphopenia may contribute to immune suppression and 
      increased risk of infection. Familiarity with these hematologic changes is 
      prudent as more patients are treated with this class of drugs.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Chen, Amy
AU  - Chen A
AD  - University of Kentucky, Lexington, KY.
FAU - Chen, Li
AU  - Chen L
AD  - University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
FAU - Al-Qaisi, Abeer
AU  - Al-Qaisi A
AD  - University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
FAU - Romond, Edward
AU  - Romond E
AD  - University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
FAU - Awasthi, Mukta
AU  - Awasthi M
AD  - University of Kentucky, Lexington, KY.
FAU - Kadamyan-Melkumyan, Vera
AU  - Kadamyan-Melkumyan V
AD  - University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
FAU - Massarweh, Suleiman
AU  - Massarweh S
AD  - University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY. 
      Electronic address: massarweh@uky.edu.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140815
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Anemia/chemically induced/epidemiology
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*blood/*drug therapy/epidemiology/pathology
MH  - Erythrocyte Count
MH  - Erythrocyte Indices
MH  - Estradiol/administration & dosage/analogs & derivatives
MH  - Everolimus
MH  - Female
MH  - Fulvestrant
MH  - Hematologic Diseases/*chemically induced/epidemiology
MH  - Humans
MH  - Leukocyte Count
MH  - Leukopenia/chemically induced/epidemiology
MH  - Neoplasm Metastasis
MH  - Sirolimus/administration & dosage/adverse effects/*analogs & derivatives
MH  - Thrombocytopenia/chemically induced/epidemiology
OTO - NOTNLM
OT  - Anemia
OT  - Lymphopenia
OT  - Microcytosis
OT  - Thrombocytopenia
OT  - mTOR
EDAT- 2014/09/10 06:00
MHDA- 2015/10/02 06:00
CRDT- 2014/09/10 06:00
PHST- 2014/05/20 00:00 [received]
PHST- 2014/07/09 00:00 [accepted]
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2015/10/02 06:00 [medline]
AID - S1526-8209(14)00155-4 [pii]
AID - 10.1016/j.clbc.2014.07.002 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2015 Feb;15(1):48-53. doi: 10.1016/j.clbc.2014.07.002. Epub 
      2014 Aug 15.