Imatinib, sunitinib and pazopanib: From flat-fixed dosing towards a pharmacokinetically guided personalized dose

Autor: Westerdijk, K., Desar, I.M.E., Steeghs, N., Graaf, W.T.A. van der, Erp, N.P. van, Huitema, A.D.R., Mathijssen, A.H.J., Gelderblom, A.J., Reyners, A.K.L., Koolen, S.L.W., Moes, D.J.A.R., Touw, D.J., DPOG
Rok vydání: 2020
Předmět:
Oncology
Review
030226 pharmacology & pharmacy
Tyrosine-kinase inhibitor
0302 clinical medicine
PHASE-I TRIAL
RENAL-CELL CARCINOMA
Sunitinib
Pharmacology (medical)
030212 general & internal medicine
Sulfonamides
medicine.diagnostic_test
GASTROINTESTINAL STROMAL TUMORS
POPULATION PHARMACOKINETICS
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
Imatinib Mesylate
Drug Monitoring
TYROSINE KINASE INHIBITOR
pharmacokinetics
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
medicine.drug
PROGRESSION-FREE SURVIVAL
medicine.medical_specialty
Indazoles
medicine.drug_class
therapeutic drug monitoring
ACTIVE METABOLITE
Reviews
Antineoplastic Agents
Pazopanib
03 medical and health sciences
Pharmacokinetics
Internal medicine
medicine
pharmacodynamics
Humans
Progression-free survival
CHRONIC MYELOID-LEUKEMIA
Protein Kinase Inhibitors
ACUTE LYMPHOBLASTIC-LEUKEMIA
Pharmacology
business.industry
Imatinib
anticancer drugs
Pyrimidines
Therapeutic drug monitoring
Pharmacodynamics
ENDOTHELIAL GROWTH-FACTOR
business
Zdroj: British Journal of Clinical Pharmacology, 86, 258-273
British Journal of Clinical Pharmacology, 86(2), 258-273. WILEY
British Journal of Clinical Pharmacology
British Journal of Clinical Pharmacology, 86, 2, pp. 258-273
ISSN: 0306-5251
Popis: Contains fulltext : 218191.pdf (Publisher’s version ) (Open Access) Tyrosine kinase inhibitors (TKIs) are anti-cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure-treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib.
Databáze: OpenAIRE
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