title: Elevated total iron-binding capacity as a predictor of response to deferasirox therapy in the setting of chronic iron overload.
abstract: It is difficult to predict the efficacy of deferasirox (DFX) as its pharmacokinetics varies among patients. The area under the curve (AUC) is reportedly useful for determining adequate DFX dosage; however, serum concentration measurements are often challenging. Effective DFX dosage is thus defined by assessing the efficacy of this agent in clinical practice. To analyze a predictive response marker to DFX therapy for use in adjusting the effective dosage during the early treatment phase, we retrospectively evaluated 39 DFX-treated patients. We defined response as a >40 % decrease in serum ferritin concentration from the pretreatment level. A maximum elevation of the total iron-binding capacity (TIBC) correlated with response in a multivariate analysis of iron metabolic markers (R (2) = 0.37, p < 0.001). A receiver operating characteristic curve analysis revealed that TIBC elevation had an AUC of 0.85 (p < 0.001) and the optimal cut-off value of TIBC elevation was 150 µg/dl. TIBC elevation of >150 µg/dl is a favorable predictor of effective ferritin reduction in DFX therapy (hazard ratio 29.6, 95 % confidence interval 4.8-183.6; p < 0.001). DFX therapy with TIBC monitoring may enable the determination of the minimum effective DFX dosage.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan, dri3001@ndmc.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Watanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kato
authors.forename: Reina
authors.initials: R
authors.lastname: Hikota
authors.forename: Takaaki
authors.initials: T
authors.lastname: Maekawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Ayako
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Osawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kimura
mesh_terms: D001565:Benzoates / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism*; D000077588:Deferasirox; D016903:Drug Monitoring; D005260:Female; D005293:Ferritins / Q000097:blood*; D019337:Hematologic Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011485:Protein Binding; D012372:ROC Curve; D012189:Retrospective Studies; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D001798:Blood Proteins; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox