Macrocytosis as a potential parameter associated with survival after tyrosine kinase inhibitor treatment

Eur J Cancer. 2016 Mar;56:101-106. doi: 10.1016/j.ejca.2015.12.019. Epub 2016 Feb 1.

Abstract

Aim of the study: 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.

Materials and 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).

Conclusion: 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.

Keywords: Cancer; Macrocytosis; Predictive marker; Targeted therapy; Tyrosine kinase inhibitors.

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / mortality
  • Disease-Free Survival
  • Erythrocyte Indices
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Indoles / adverse effects*
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / mortality
  • Male
  • Molecular Targeted Therapy
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / adverse effects*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrroles / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Sunitinib
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Hemoglobins
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Protein-Tyrosine Kinases
  • Sunitinib