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

Antonio Piga, Renzo Galanello, Gian Luca Forni, Maria Domenica Cappellini, Raffaella Origa, Antonietta Zappu, Guido Donato, Elena Bordone, Antonella Lavagetto, Laura Zanaboni, Romain Sechaud, Nicola Hewson, John M. Ford, Herbert Opitz, Daniele Albert

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. 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. Design and 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. Interpretation and 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.

Original languageEnglish
Pages (from-to)873-880
Number of pages8
JournalHaematologica
Volume91
Issue number7
Publication statusPublished - Jul 2006

Keywords

  • Deferasirox
  • Deferoxamine
  • Efficacy
  • Iron chelation
  • Thalassemia
  • Well tolerated

ASJC Scopus subject areas

  • Hematology

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