title: Management of dose variability and side effects for individualized cancer pharmacotherapy with tyrosine kinase inhibitors.
abstract: Molecular-targeted therapies with tyrosine kinase inhibitors (TKIs) have provided a major breakthrough in cancer treatment. These agents are given orally and demonstrated to be substrates for drug transporters. In clinical settings, TKIs are mainly used at a fixed dose, but wide interpatient variability has been observed in their pharmacokinetics and/or pharmacodynamics. Genetic polymorphisms of ABC transporters, drug-drug interaction and adherence are among the factors causing such variation. To overcome these problems, therapeutic drug monitoring has been applied in clinical practice for patient care. Skin disorders are frequently observed as adverse drug reactions when using TKIs, and are commonly managed by symptomatic therapy based on clinical experience. Recent studies have provided some insights into the molecular mechanisms underlying skin disorders induced by TKIs. This review article summarizes the accumulated clinical and basic pharmacological evidence of TKIs, focusing on erlotinib, sorafenib and sunitinib.
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu City, Shiga 520-2192, Japan. Electronic address: teradat@belle.shiga-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu City, Shiga 520-2192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noda
authors.affiliation: Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Kyoto, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: Drug interaction; Drug transporter; Skin disorders; Therapeutic drug monitoring; Tyrosine kinase inhibitors