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.
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: R J Bergeron; G W Yao; H Yao; W R Weimar; C A Sninsky; B Raisler; Y Feng; Q Wu; F Gao Journal: J Med Chem Date: 1996-06-21 Impact factor: 7.446
Authors: R J Bergeron; J Wiegand; J S McManis; W R Weimar; R E Smith; S E Algee; T L Fannin; M A Slusher; P S Snyder Journal: J Med Chem Date: 2001-01-18 Impact factor: 7.446
Authors: Hillary A Hahm; David S Ettinger; Kathy Bowling; Beth Hoker; Tian Ling Chen; Yelena Zabelina; Robert A Casero Journal: Clin Cancer Res Date: 2002-03 Impact factor: 12.531
Authors: R R Love; R Jacoby; M A Newton; K D Tutsch; K Simon; M Pomplun; A K Verma Journal: Cancer Epidemiol Biomarkers Prev Date: 1998-11 Impact factor: 4.254
Authors: Dong Joon Kim; Eunmiri Roh; Mee-Hyun Lee; Naomi Oi; Do Young Lim; Myoung Ok Kim; Young-Yeon Cho; Angelo Pugliese; Jung-Hyun Shim; Hanyong Chen; Eun Jin Cho; Jong-Eun Kim; Sun Chul Kang; Souren Paul; Hee Eun Kang; Ji Won Jung; Sung-Young Lee; Sung-Hyun Kim; Kanamata Reddy; Young Il Yeom; Ann M Bode; Zigang Dong Journal: Cancer Res Date: 2015-12-16 Impact factor: 12.701