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


CONCLUSIONS
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.
Wilding
George
G
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792, USA.
King
David
D
Tutsch
Kendra
K
Pomplun
Marcia
M
Feierabend
Chris
C
Alberti
Dona
D
Arzoomanian
Rhoda
R
D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D011073:Polyamines / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D013096:Spermine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*
D011073:Polyamines; C058306:N(1),N(14)-bis(ethyl)homospermine; D013096:Spermine