Homoharringtonine: a phase I evaluation

Invest New Drugs. 1985;3(3):279-86. doi: 10.1007/BF00179432.

Abstract

Homoharringtonine is one of several Cephalotaxine esters which have shown experimental antineoplastic activity as well as anti-leukemia effects in patients in China. In a Phase I trial of homoharringtonine administered daily X 5 by bolus intravenous injection, the dose limiting toxicity was hypotension and the maximum tolerated dose was 3.5 mg/m2/d X 5. Evidence of drug induced cardiac irritability with resulting ventricular and atrial dysrhythmias was seen. Minimal myelosuppression was seen at this dose. Treatment of patients by 5 day continuous intravenous (rather than bolus) infusion resulted in more pronounced myelosuppression and clinically significant but tolerable hypotension. Significant reduction of white blood cell and platelet counts occurred at a dose of 3.5 mg/m2/day. Further investigations of the hypotensive and cardiac effects of homoharringtonine and Phase II trials using continuous infusion are indicated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alkaloids / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Drug Evaluation
  • Female
  • Harringtonines / administration & dosage
  • Harringtonines / adverse effects
  • Harringtonines / therapeutic use*
  • Heart / drug effects
  • Homoharringtonine
  • Humans
  • Infusions, Parenteral
  • Leukocyte Count / drug effects
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Platelet Count / drug effects
  • Time Factors

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Harringtonines
  • Homoharringtonine