title: A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.
abstract: Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.
authors.affiliation: Fondazione Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena IRCCS, Universita di Milano, Via F. Sforza 35, 20122 Milan, Italy. maria.cappellini@unimi.it
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Alan
authors.initials: A
authors.lastname: Cohen
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.forename: Leyla
authors.initials: L
authors.lastname: Agaoglu
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Yurdanur
authors.initials: Y
authors.lastname: Kilinc
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Marcello
authors.initials: M
authors.lastname: Capra
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Slaheddine
authors.initials: S
authors.lastname: Fattoum
authors.forename: Guillermo
authors.initials: G
authors.lastname: Drelichman
authors.forename: Carmelo
authors.initials: C
authors.lastname: Magnano
authors.forename: Monica
authors.initials: M
authors.lastname: Verissimo
authors.forename: Miranda
authors.initials: M
authors.lastname: Athanassiou-Metaxa
authors.forename: Patricia
authors.initials: P
authors.lastname: Giardina
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kourakli-Symeonidis
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka-Schaub
authors.forename: Thomas
authors.initials: T
authors.lastname: Coates
authors.forename: Christiane
authors.initials: C
authors.lastname: Vermylen
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thuret
authors.forename: Herbert
authors.initials: H
authors.lastname: Opitz
authors.forename: Catherine
authors.initials: C
authors.lastname: Ressayre-Djaffer
authors.forename: Peter
authors.initials: P
authors.lastname: Marks
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012449:Safety; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox