title: Macrocytosis as a potential parameter associated with survival after tyrosine kinase inhibitor treatment.
abstract: OBJECTIVE
  As a rise in mean corpuscular volume (MCV) of the erythrocyte is frequently seen during treatment with imatinib and sunitinib, we investigated whether macrocytosis (MCV > 100 fl) also occurs as a class effect in other tyrosine kinase inhibitors (TKIs) and whether occurrence of macrocytosis is associated with outcome.
  
  
  METHODS
  In 533 patients, using 5 TKIs, we investigated if macrocytosis and an increase in MCV were associated with progression-free survival and overall survival (OS) in specific tumour-treatment combinations.
  
  
  RESULTS
  Macrocytosis as well as an increase in MCV from baseline of >10 fl (ΔMCV +10 fl), when included as a time-dependent covariate, were associated with improved OS in patients with renal cell cancer (RCC) treated with sunitinib (macrocytosis, hazard ratio [HR] = 0.61, p = 0.031, and ΔMCV +10 fl, HR = 0.58, p = 0.016).
  
  
  CONCLUSIONS
  In sunitinib-treated patients with RCC, the occurrence of macrocytosis, or a substantial increase in MCV levels after start of treatment, could potentially serve as a positive prognostic factor for survival, if validated prospectively.
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Jacqueline S L
authors: JSL
authors: Kloth
authors: Dept of Internal Medicine, Sint Franciscus Gasthuis, Kleiweg 500, 3045 PM, Rotterdam, The Netherlands.
authors: Paul
authors: P
authors: Hamberg
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Pauline A J
authors: PAJ
authors: Mendelaar
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Roderick R
authors: RR
authors: Dulfer
authors: Clinical Trial Center, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Bronno
authors: B
authors: van der Holt
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Karel
authors: K
authors: Eechoute
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Erik A C
authors: EAC
authors: Wiemer
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Wim H J
authors: WHJ
authors: Kruit
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors: Stefan
authors: S
authors: Sleijfer
authors: Dept of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands. Electronic address: a.mathijssen@erasmusmc.nl.
authors: Ron H J
authors: RHJ
authors: Mathijssen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D018572:Disease-Free Survival; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D008297:Male; D058990:Molecular Targeted Therapy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D000077210:Sunitinib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib
keywords: Cancer; Macrocytosis; Predictive marker; Targeted therapy; Tyrosine kinase inhibitors