Efficacy and toxicity of IFN-alpha2b combined with cytarabine in chronic myelogenous leukaemia

Br J Haematol. 1999 Sep;106(4):1013-9. doi: 10.1046/j.1365-2141.1999.01662.x.

Abstract

Newly diagnosed chronic myelogenous leukaemia (CML) patients (n = 65) were treated with interferon (IFN)-alpha2b (5 x 106 IU/d s.c.) combined with monthly courses of cytarabine (20 mg/d s.c. for 14 d). Median age of patients enrolled was 45 years. The endpoints of the study were clinical efficacy and toxicity. The survival rates at 3 years and 5 years were 77% and 56%, respectively. The rate of complete haematological response was 60%. Evaluation of cytogenetic response was available in 29/65 patients. A complete cytogenetic response was seen in 3/29 patients (10%). W.H.O. toxicity grade 3-4 occurred in only 22/523 evaluable treatment cycles. Since the study protocol required intermittent or definitive discontinuation of cytarabine in case of moderate leucopenia (white blood cells (WBC) <5 x 109/l), combined cytopenia (WBC < 5 x 109/l, platelets <100 x 109/l), and isolated moderate thrombocytopenia (<100 x 109/l), the drug had to be discontinued temporarily or definitively in 200 cycles and the dose of cytarabine had to be reduced in 35 cycles. Thus, only 25% of the planned dose of cytarabine could be administered. At this dosage it would appear that cytarabine had no effect on survival and did not improve remission rates. We conclude that a clinical benefit for the addition of cytarabine to the treatment of CML with IFN might only be achieved by the administration of a higher cumulative dose of cytarabine, suggesting that lower leucocyte counts of 2-4 x 109/l have to be tolerated.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage*
  • Cytarabine / adverse effects
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Pain / chemically induced
  • Recombinant Proteins
  • Survival Analysis
  • Treatment Outcome

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Cytarabine