Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial

Nisbet-Brown, Eric; Olivieri, Nancy F.; Giardina, Patricia J.; Grady, Robert W.; Neufeld, Ellis J.; Séchaud, Romain; Krebs-Brown, Axel; Anderson, Judith; Alberti, Daniele; Sizer, Kurt C.; Nathan, David G.

doi:10.1016/s0140-6736(03)13309-0

Cited by 300 publications

(266 citation statements)

References 20 publications

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“…The most frequent adverse events with suspected relationship to repeated administration of deferasirox consisted of transient WHO grades I-II gastrointestinal symptoms such as nausea and diarrhea, similarly found in other studies [18,21,39,40]. These common side effects may be partly caused by the presence of lactose in the formulation of deferasirox [33] and did not require treatment discontinuation in our patients.…”

Section: Discussionsupporting

confidence: 86%

“…Deferasirox binds iron in a 2:1 ratio before being excreted primarily in the bile [15]. A series of studies have demonstrated its efficacy and safety in patients with thalassemia major in a daily dose ranging between 20 and 30 mg/kg [12,[16][17][18][19][20][21]. So far, experiences regarding treatment with deferasirox in individuals with diseases other than thalassemia are only limited [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

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International audienceBlood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade®) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53–91) were enrolled. Deferasirox administered in a once-daily dose of 20–30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 µg/L (range 665–6,900) to 413 µg/L (range 105–3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 µmol/g ( = 0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine β2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

et al. 2008

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“…Although hematopoietic cell transplantation is the only proven curative therapy for SCD, other treatments such as oral hydroxyurea, 48,49 novel transfusion strategies 50 or oral chelators 51 pose fewer short-term risks and could be considered in some children with SCD. Additional studies of UPBCT for SCD are warranted but should be undertaken with caution as we learn more about the factors that predict outcomes of UPBCT and as nontransplant therapies for SCD evolve and mature.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease

Adamkiewicz

Mehta

Boyer

et al. 2004

Bone Marrow Transplant

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“…The primary findings in Phase I and II studies of deferasirox were dose-related increases in iron excretion and the absence of significant acute side effects other than gastrointestinal disturbances that were generally mild and a diffuse rash that appeared to be more common at higher doses. 24 The Phase III or pivotal study of deferasirox enrolled 586 patients with thalassemia in 65 sites and was designed to test non-inferiority to deferoxamine. 25 The primary endpoint was built around the change in liver iron concentration as measured by biochemical analysis of liver biopsies in most patients and by biomagnetic liver susceptometry (SQUID) in a subset of patients.…”

Section: Deferasiroxmentioning

confidence: 99%

New Advances in Iron Chelation Therapy

Cohen

2006

Hematology

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The emergence of new chelators is likely to have a major impact on the treatment of thalassemia major, sickle cell disease and other hematologic disorders for which regular red cell transfusions are required either to correct severe anemia or to prevent major complications of the underlying disease. In comparison with deferoxamine, which requires prolonged parenteral infusion to achieve negative iron balance, orally active chelators offer the promise of easier administration and better compliance. Moreover, the availability of more than one iron chelator opens up the possibility of combination therapy to target iron in specific organs and to enhance overall iron excretion. Long-term studies, employing new technologies to measure tissue iron, are required to determine whether the new chelators will be as safe and effective as deferoxamine in maintaining control of iron stores and preventing iron-induced cardiac disease, the major complication of transfusional iron overload.

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Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial

Cited by 300 publications

References 20 publications

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease

New Advances in Iron Chelation Therapy

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