Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload.
OBJECTIVE
Iron accumulation is an inevitable consequence of chronic blood transfusions and results in serious complications in the absence of chelation treatment to remove excess iron. Deferoxamine (Desferal, DFO) reduces morbidity and mortality although the administration schedule of slow, parenteral infusions several days each week limits compliance and negatively affects long-term outcome. Deferasirox (Exjade, ICL670) is an oral chelator with high iron-binding potency and selectivity. In a phase II study, the tolerability and efficacy of deferasirox were compared with those of DFO in 71 adults with transfusional hemosiderosis.


METHODS
Patients were randomized to receive once-daily deferasirox (10 or 20 mg/kg; n=24 in both groups) or DFO (40 mg/kg, 5 days/week; n=23) for 48 weeks. Results. Both treatments were well tolerated and no patient discontinued deferasirox due to drug-related adverse events. The reported frequency of transient, mild to moderate gastrointestinal disturbances was higher in the deferasirox group than in the DFO group, but these disturbances settled spontaneously without dose interruption in all patients. Decreases in liver iron concentration (LIC) were comparable in the deferasirox 20 mg/kg/day and DFO groups; baseline values of 8.5 and 7.9 mg Fe/g dw fell to 6.6 and 5.9 mg Fe/g dw, respectively, by week 48. Deferasirox showed a plasma elimination half-life of 8-16 hours, supporting its once-daily administration.


CONCLUSIONS
Deferasirox at daily doses of 10 or 20 mg/kg was well tolerated and, at 20 mg/kg, showed similar efficacy to DFO 40 mg/kg in terms of decreases in LIC.
Piga
Antonio
A
Centro Microcitemie, Divisione di Ematologia Pediatrica, Dipartimento di Scienze Pediatriche, Università di Torino, Italy. antonio.piga@unito.it
Galanello
Renzo
R
Forni
Gian Luca
GL
Cappellini
Maria Domenica
MD
Origa
Raffaella
R
Zappu
Antonietta
A
Donato
Guido
G
Bordone
Elena
E
Lavagetto
Antonella
A
Zanaboni
Laura
L
Sechaud
Romain
R
Hewson
Nicola
N
Ford
John M
JM
Opitz
Herbert
H
Alberti
Daniele
D
D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019190:Iron Overload / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017086:beta-Thalassemia / Q000150:complications / Q000628:therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D003676:Deferoxamine; D000077588:Deferasirox