Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study.
OBJECTIVE
Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20-30 mg/kg/d reduces iron burden, depending on transfusional iron intake.


METHODS
The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients > or =2 yr with beta-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of > or =3 mg Fe/g dry weight (dw) if baseline LIC was > or =10 mg Fe/g dw, or final LIC of 1-7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw.


RESULTS
Overall, 233/237 enrolled patients completed 1 yr's treatment. Mean baseline LIC was 18.0 +/- 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr's deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment.


CONCLUSIONS
The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with beta-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden.
Taher
Ali
A
Department of Internal Medicine, Hematology, Oncology Division, American University of Beirut Medical Center, Beirut, Lebanon. ataher@aub.edu.lb
El-Beshlawy
Amal
A
Elalfy
Mohsen S
MS
Al Zir
Kusai
K
Daar
Shahina
S
Habr
Dany
D
Kriemler-Krahn
Ulrike
U
Hmissi
Abdel
A
Al Jefri
Abdullah
A
D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects; D002675:Child, Preschool; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000032:analysis; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019190:Iron Overload / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry; D008297:Male; D011728:Pyridones; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult; D017086:beta-Thalassemia / Q000188:drug therapy*
D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox