title: A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.
abstract: Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.
authors.affiliation: Children's Hospital and Research Center, Oakland, CA 94609, USA. evichinsky@mail.cho.org
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: Onyinye
authors.initials: O
authors.lastname: Onyekwere
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Paul
authors.initials: P
authors.lastname: Swerdlow
authors.forename: James
authors.initials: J
authors.lastname: Eckman
authors.forename: Peter
authors.initials: P
authors.lastname: Lane
authors.forename: Beatrice
authors.initials: B
authors.lastname: Files
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hassell
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Felicia
authors.initials: F
authors.lastname: Wilson
authors.forename: Françoise
authors.initials: F
authors.lastname: Bernaudin
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Iheanyi
authors.initials: I
authors.lastname: Okpala
authors.forename: Catherine
authors.initials: C
authors.lastname: Ressayre-Djaffer
authors.forename: Daniele
authors.initials: D
authors.lastname: Alberti
authors.forename: Jaymes
authors.initials: J
authors.lastname: Holland
authors.forename: Peter
authors.initials: P
authors.lastname: Marks
authors.forename: Ellen
authors.initials: E
authors.lastname: Fung
authors.forename: Roland
authors.initials: R
authors.lastname: Fischer
authors.forename: Brigitta U
authors.initials: BU
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Coates
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007501:Iron / Q000032:analysis / Q000097:blood; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry; D008297:Male; D012141:Respiratory Tract Infections / Q000139:chemically induced; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000410:Alanine Transaminase; D003676:Deferoxamine; D000077588:Deferasirox