title: Everolimus-induced hematologic changes in patients with metastatic breast cancer.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Kentucky, Lexington, KY.
authors.forename: Amy
authors.initials: A
authors.lastname: Chen
authors.affiliation: University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
authors.forename: Abeer
authors.initials: A
authors.lastname: Al-Qaisi
authors.affiliation: University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
authors.forename: Edward
authors.initials: E
authors.lastname: Romond
authors.affiliation: University of Kentucky, Lexington, KY.
authors.forename: Mukta
authors.initials: M
authors.lastname: Awasthi
authors.affiliation: University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
authors.forename: Vera
authors.initials: V
authors.lastname: Kadamyan-Melkumyan
authors.affiliation: University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY. Electronic address: massarweh@uky.edu.
authors.forename: Suleiman
authors.initials: S
authors.lastname: Massarweh
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068338:Everolimus; D005260:Female; D000077267:Fulvestrant; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology; D009362:Neoplasm Metastasis; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000077267:Fulvestrant; D004958:Estradiol; D000068338:Everolimus; D020123:Sirolimus
keywords: Anemia; Lymphopenia; Microcytosis; Thrombocytopenia; mTOR