Phase I trial of the polyamine analog N1,N14-diethylhomospermine (DEHSPM) in patients with advanced solid tumors.

Abstract

BACKGROUND:

This phase I study was conducted to determine maximal tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients with advanced solid tumors treated with the polyamine analog N1, N14-diethylhomospermine (DEHSPM).

METHODS:

Patients were treated with DEHSPM administered as a subcutaneous (SC) injection daily for five consecutive days repeated every 4 weeks. Three dose levels were examined starting at 12.5 mg/m2/day, escalating to 37.5 mg/m2/day.

RESULTS:

A total of 15 patients were enrolled. Dose limiting toxicities (grade 3 or 4) included nausea, vomiting, constipation, ileus, elevations of aspartate aminotransferase (AST) and alkaline phosphatase, hyperbilirubinemia, and ventricular bigeminy.

CONCLUSION:

DEHSPM given as a SC injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. MTD was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses.

• Authors: George Wilding, David King, Kendra Tutsch, Marcia Pomplun, Chris Feierabend, Dona Alberti, Rhoda Arzoomanian
• Journal: Investigational new drugs (Invest New Drugs) Vol. 22 Issue 2 Pg. 131-8 (Apr 2004) ISSN: 0167-6997 [Print] United States
• PMID: 14739661 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Polyamines
• N(1),N(14)-bis(ethyl)homospermine
• Spermine

Topics

• Aged
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Gastrointestinal Diseases (blood, chemically induced)
• Humans
• Male
• Middle Aged
• Neoplasms (blood, drug therapy)
• Polyamines (blood, chemistry, therapeutic use)
• Spermine (adverse effects, analogs & derivatives, blood, therapeutic use)