title: A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia.
abstract: This prospective randomized phase II study aimed to determine the safety and efficacy of deferasirox in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for acute myeloid leukaemia (AML) ize. Serum ferritin, transferrin saturation and CRP were measured pre-, mid- and post- each chemotherapy cycle. Patients were randomized to receive either therapy with deferasirox vs. no deferasirox therapy once serum ferritin increased to >500 μg/l. The trial was stopped prematurely due to excess gastrointestinal (GI) and infectious toxicity demonstrable in the deferasirox arm, after 10 patients had been randomized to deferasirox and 6 patients to the control arm. Overall, deferasirox was poorly tolerated, with median maximum tolerated dose only 13·8 mg/kg/d and no patient able to tolerate doses >20 mg/kg/d. Median duration of deferasirox therapy was only 72 d (range 19-130 d), with 9/10 patients requiring unplanned dose interruptions and 4/10 patients unable to continue the drug predominantly due to GI effects. Although all 3 treatment-related deaths occurred in the deferasirox arm (P = 0·25), median overall survival was similar between treatment arms. Use of deferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is poorly tolerated and appears to be associated with excess GI and infectious toxicity.
authors.affiliation: Department of Haematology, Royal Brisbane and Women's Hospital, Butterfield St, Herston, QLD 4029, Australia. glen_kennedy@health.qld.gov.au
authors.forename: Glen A
authors.initials: GA
authors.lastname: Kennedy
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Morris
authors.forename: Elango
authors.initials: E
authors.lastname: Subramonpillai
authors.forename: Cameron
authors.initials: C
authors.lastname: Curley
authors.forename: Jason
authors.initials: J
authors.lastname: Butler
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
mesh_terms: D000328:Adult; D000368:Aged; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060830:Consolidation Chemotherapy; D000077588:Deferasirox; D057239:Early Termination of Clinical Trials; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007049:Iatrogenic Disease; D060828:Induction Chemotherapy; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D000077588:Deferasirox