Phase I trial of the polyamine analog N1,N14-diethylhomospermine (DEHSPM) in patients with advanced solid tumors
| Autor: | Chris Feierabend, David M. King, Dona Alberti, Marcia Pomplun, Rhoda Z. Arzoomanian, Kendra D. Tutsch, George Wilding |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Constipation Ileus Nausea Gastrointestinal Diseases Diethylhomospermine Gastroenterology Drug Administration Schedule chemistry.chemical_compound Internal medicine Neoplasms medicine Polyamines Humans Pharmacology (medical) Aged Pharmacology Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Oncology chemistry Bigeminy Anesthesia Vomiting Alkaline phosphatase Female Spermine medicine.symptom business Polyamine |
| Zdroj: | Investigational new drugs. 22(2) |
| ISSN: | 0167-6997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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