Induction therapy of AML with ara-C plus daunorubicin versus ara-C plus gemtuzumab ozogamicin: a randomized phase II trial in elderly patients

Ann Oncol. 2012 Apr;23(4):990-6. doi: 10.1093/annonc/mdr346. Epub 2011 Aug 2.

Abstract

Background: Chemotherapy for elderly patients with acute myeloid leukemia (AML) results in a median overall survival (OS) of ≤ 1 year. Elderly patients often present with cardiac comorbidity. Gemtuzumab ozogamicin (GO) is active in elderly (≥ 60 years) patients with relapsed AML with low cardiac toxicity.

Patients and methods: This randomized phase II study compared a standard combination of ara-C and daunorubicin (DNR; 7+3) versus ara-C plus gemtuzumab ozogamicin (7+GO) as the first course of induction therapy. Primary objectives were comparison of blast clearance on day 16, event-free survival (EFS), and remission duration. OS, complete remission (CR), and tolerability were secondary objectives.

Results: One hundred and nineteen patients with de novo AML, treatment-related AML, AML with a history of myelodysplastic syndrome (MDS), or high-risk MDS entered the study. Median age of 115 patients (intent-to-treat population) was 69 years. Protocol outlined a second course 7+3 for patients without blast clearance and two courses of high-dose ara-C consolidation upon CR. Both treatments were equally effective in blast clearance, CR, EFS, remission duration, or OS (median: 7+3, 9 months; 7+GO, 10 months). Induction death rate was higher in the GO group due to veno-occlusive disease.

Conclusion: The study did not show significant superiority of 7+GO over standard 7+3.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Disease-Free Survival
  • Female
  • Gemtuzumab
  • Humans
  • Induction Chemotherapy*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Survival Analysis
  • Treatment Outcome

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Cytarabine
  • Gemtuzumab
  • Daunorubicin