A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804

Cancer Chemother Pharmacol. 2009 Apr;63(5):859-64. doi: 10.1007/s00280-008-0805-8. Epub 2008 Aug 1.

Abstract

Background: Both homoharringtonine (HHT), an alkaloid derivative from the Chinese yew tree that inhibits protein synthesis, and low-dose cytarabine have independent activity in CML and have been used in combination after failure of interferon therapy.

Patients and methods: The CALGB performed a phase II trial of HHT (2.5 mg/m(2) per day) plus cytarabine (7.5 mg/m(2) per day), given together via continuous intravenous infusion for 7 days in previously untreated patients with Ph chromosome positive chronic phase CML. HHT/cytarabine cycles were repeated every 28 days if the blood counts were adequate. The primary endpoint was the major cytogenetic response rate after 9 months.

Results: Forty of the 44 enrolled patients required reduction in the infusion duration during at least one cycle. Myelosuppression was common; 66% developed neutrophil count <500/microl, but grade 3 infections occurred in only 7%. Thirty-six of 44 patients (82%) achieved a complete hematologic remission; the median duration has not been reached. Only 4 of the 23 patients (17%) having adequate cytogenetic response assessment achieved a major response within nine cycles.

Conclusions: Although HHT/cytarabine was generally well tolerated, the cytogenetic response rate did not exceed the level previously seen in patients with interferon-refractory CML and was not nearly as high as associated with imatinib in newly diagnosed patients.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Female
  • Harringtonines / administration & dosage
  • Homoharringtonine
  • Humans
  • Infusions, Intravenous
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / diagnosis
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Palliative Care
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Harringtonines
  • Cytarabine
  • Homoharringtonine