title: Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy does not improve remission rates in patients with primary refractory acute myeloid leukemia in a randomized phase II study.
abstract: BACKGROUND
  XIAP (X-linked inhibitor of apoptosis protein) is an inhibitor of caspases 3 and 9 that is overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report an open-label randomized phase II trial of reinduction chemotherapy with and without the XIAP antisense oligonucleotide AEG35156 in patients with AML who did not achieve remission with initial induction chemotherapy.
  
  
  METHODS
  Twenty-seven patients with AML who were refractory to initial induction chemotherapy were randomized and treated with AEG35156 (650 mg) in combination with high-dose cytarabine and idarubicin. Thirteen patients were randomized and treated with high-dose cytarabine and idarubicin alone. The rates of response and toxicity were determined.
  
  
  RESULTS
  Of the 27 patients assigned to AEG35156 in combination with high-dose cytarabine and idarubicin, 3 died during reinduction chemotherapy, 5 achieved complete remission (CR), and 6 achieved CR with incomplete platelet count recovery (CRp), for an overall response rate of 41%. Of the 13 patients assigned to the control arm of the study, none died during reinduction, 6 achieved CR, and 3 achieved CRp, for an overall response rate of 69%. The differences in response rates between patients in the AEG35156 and control arms were not statistically different (P = 0.18 by the χ(2) test).
  
  
  CONCLUSIONS
  The addition of AEG35156 to reinduction chemotherapy was well tolerated but did not improve rates of remission. Therefore alternative therapeutic strategies should be explored in patients with AML refractory to induction chemotherapy.
authors: Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Canada. aaron.schimmer@utoronto.ca
authors: Aaron D
authors: AD
authors: Schimmer
authors: Wolfgang
authors: W
authors: Herr
authors: Mathias
authors: M
authors: Hänel
authors: Gautham
authors: G
authors: Borthakur
authors: Arthur
authors: A
authors: Frankel
authors: Heinz-August
authors: HA
authors: Horst
authors: Sonja
authors: S
authors: Martin
authors: Jeannine
authors: J
authors: Kassis
authors: Pierre
authors: P
authors: Desjardins
authors: Karen
authors: K
authors: Seiter
authors: Walter
authors: W
authors: Fiedler
authors: Richard
authors: R
authors: Noppeney
authors: Aristoteles
authors: A
authors: Giagounidis
authors: Christine
authors: C
authors: Jacob
authors: Jacques
authors: J
authors: Jolivet
authors: Martin S
authors: MS
authors: Tallman
authors: Steffen
authors: S
authors: Koschmieder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage*; D012074:Remission Induction; D016896:Treatment Outcome; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D055815:Young Adult
chemical_list: C498209:AEG 35156; D009841:Oligonucleotides; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human