Adverse effects of dasatinib on glucose-lipid metabolism in patients with chronic myeloid leukaemia in the chronic phase

Sci Rep. 2019 Nov 26;9(1):17601. doi: 10.1038/s41598-019-54033-0.

Abstract

To explore the differences in glucose-lipid metabolism profiles among the 3 TKIs, we designed a retrospective study to compare the onset of hyperglycaemia, hypertriglyceridemia, hypercholesterolemia and hyper-low density lipoprotein (LDL)-cholesterolemia in the patients with normal baseline glucose-lipid profiles and had no medical record of cardio- or cerebro-vascular diseases and/or metabolic syndrome diseases, and identify variables associated with them. 370 chronic myeloid leukaemia patients receiving dasatinib, nilotinib or imatinib therapy ≥3 months were retrospectively reviewed. During TKI-therapy, the mean fasting glucose, triglyceride, cholesterol, and LDL-cholesterol levels increased significantly in both dasatinib and nilotinib cohorts compared with the imatinib cohort. In multivariate analyses, dasatinib was the factor significantly associated with both poor hyperglycaemia- and hypertriglyceridemia-free survival. In addition, nilotinib was significantly associated with more occurrences of hyperglycaemia and hypercholesterolemia; increasing age was significantly associated with more occurrences of hyperglycaemia and hypertriglyceridemia. We concluded that dasatinib, similar to nilotinib, has the adverse impact on glucose-lipid metabolism compared with imatinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Cholesterol, LDL / blood
  • Dasatinib / adverse effects*
  • Dasatinib / pharmacology
  • Dasatinib / therapeutic use
  • Female
  • Follow-Up Studies
  • Glucose / metabolism*
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / chemically induced
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / chemically induced
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / metabolism
  • Lipid Metabolism / drug effects*
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Salvage Therapy
  • Young Adult

Substances

  • Antineoplastic Agents
  • Cholesterol, LDL
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • nilotinib
  • Glucose
  • Dasatinib