Homoharringtonine: a phase I evaluation.

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.

• Authors: J A Stewart, I H Krakoff
• Journal: Investigational new drugs (Invest New Drugs) Vol. 3 Issue 3 Pg. 279-86 ( 1985) ISSN: 0167-6997 [Print] United States
• PMID: 4066221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Harringtonines
• Homoharringtonine

Topics

• Aged
• Alkaloids (therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Drug Evaluation
• Female
• Harringtonines (administration & dosage, adverse effects, 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