title: Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia.
abstract: BACKGROUND
  The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents.
  
  
  METHODS
  To determine whether cenersen merits testing in larger efficacy studies, an exploratory study of cenersen in combination with idarubicin either alone or with 1 of 2 doses of cytarabine was performed in first-salvage AML patients. Patients who either had failed to respond to a single induction course or had responded to induction but relapsed within 12 months were enrolled. Stopping rules based on an expected 14% complete response (CR) rate were applied to each treatment arm.
  
  
  RESULTS
  Fifty-three patients were treated, and none of the arms was terminated for lack of activity. Nearly all patients received a single course unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with incomplete platelet recovery). There was a positive trend for a better response rate with increasing intensity of chemotherapy in the patients refractory to front-line treatment compared with those who had relapsed previously. One-third (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high dose antioxidants) during treatment, and none of these responded to treatment. No unique toxicity was attributed to cenersen.
  
  
  CONCLUSIONS
  The results of this study suggested that the combination of cenersen with chemotherapy may have clinical efficacy, and additional studies are warranted to explore its full potential.
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030, USA. jcortes@mdanderson.org
authors: Jorge
authors: J
authors: Cortes
authors: Hagop
authors: H
authors: Kantarjian
authors: Edward D
authors: ED
authors: Ball
authors: John
authors: J
authors: Dipersio
authors: Jonathan E
authors: JE
authors: Kolitz
authors: Hugo F
authors: HF
authors: Fernandez
authors: Mark
authors: M
authors: Goodman
authors: Gautam
authors: G
authors: Borthakur
authors: Maria R
authors: MR
authors: Baer
authors: Meir
authors: M
authors: Wetzler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D016158:Genes, p53; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012008:Recurrence; D017211:Treatment Failure
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D003561:Cytarabine; C570305:cenersen; D015255:Idarubicin