title: Clinical pharmacology, drug-drug interactions and safety of pazopanib: a review.
abstract: In the past decade, treatment options for metastatic renal cell carcinoma and soft-tissue sarcoma have expanded. Pazopanib was discovered during the screening of compounds that suppressed vascular endothelial growth factor receptor-2 (VEGFR-2). As other tyrosine kinase inhibitors (TKI), pazopanib is not totally specific for one target since it also inhibits stem-cell factor receptor (cKIT), platelet-derived growth factor receptors (PDGFRα, β), VEGFR-1 and -3. Areas covered: Clinical pharmacology, drug-drug interactions and safety data published on pazopanib, between January 2006 and April 2016, are reviewed. Expert opinion: This new therapy has been shown to improve progression-free survival compared with previous approaches, in renal cell cancer and soft-tissue sarcoma. However, some specific sub-populations, such as elderly patients, patients with brain metastases or with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 or comorbidities, are poorly represented in pivotal pazopanib phase III studies. Pazopanib meets criteria defining therapies as candidates for therapeutic drug monitoring: large intra- and inter-patient pharmacokinetic variability, potential pharmacokinetic drug-drug interactions, pharmacokinetic/pharmacodynamic relationship and narrow therapeutic index. Knowledge of predictors that can be used to guide dosing regimens in the target population and in special populations needs to be improved.
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Boudou-Rouquette
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Camille
authors.initials: C
authors.lastname: Tlemsani
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huillard
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jouinot
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arrondeau
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.|b UMR8638 CNRS, UFR de Pharmacie , Université Paris Descartes, PRES Sorbonne Paris Cité , Paris , France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Thomas-Schoemann
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.|b UMR8638 CNRS, UFR de Pharmacie , Université Paris Descartes, PRES Sorbonne Paris Cité , Paris , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: a Department of Medical Oncology, CERIA , Paris Descartes University, AP-HP, Cochin Hospital , Paris , France.
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D011743:Pyrimidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Pazopanib; clinical pharmacology; drug-drug interactions; metabolism; renal cell carcinoma; soft-tissue sarcoma; targeted therapy; toxicity