Phase I Trial of the Polyamine Analog N1,N14-Diethylhomospermine (DEHSPM) in Patients with Advanced Solid Tumors
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- 作者：George Wilding ; David King ; Kendra Tutsch ; Marcia Pomplun ; Chris Feierabend ; Dona Alberti and Rhoda Arzoomanian
- 关键词：N1 ; N14 ; diethylhomospermine ; DEHSPM ; polyamine analog ; solid tumor
- 刊名：Investigational New Drugs
- 出版年：2004
- 出版时间：2004
- 年：2004
- 卷：22
- 期：2
- 页码：131-138
- 全文大小：125 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Pharmacology and Toxicology - 出版者：Springer Netherlands
- ISSN：1573-0646
文摘
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 12.5mg/m2/day, escalating to 37.5mg/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 25mg/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.