title: Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents.
  
  
  METHODS
  A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment.
  
  
  RESULTS
  A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib.
  
  
  CONCLUSIONS
  Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio 44195, USA. rinib2@ccf.org
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Mohamad K
authors.initials: MK
authors.lastname: Khasawneh
authors.forename: Claudiu
authors.initials: C
authors.lastname: Cotta
authors.forename: Jaya
authors.initials: J
authors.lastname: Unnithan
authors.forename: Laura
authors.initials: L
authors.lastname: Wood
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.forename: Jorge
authors.initials: J
authors.lastname: Garcia
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000748:Anemia, Macrocytic / Q000139:chemically induced* / Q000453:epidemiology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D004909:Erythrocyte Indices; D005260:Female; D006403:Hematologic Tests; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D018570:Risk Assessment; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib