Antitumor efficacy of N1,N11-diethylnorspermine on a human bladder tumor xenograft in nude athymic mice

• Published in: Clinical cancer research 1997-08, Vol.3 (8), p.1239-1244
• Main Authors: SHARMA, A, GLAVES, D, PORTER, C. W, RAGHAVAN, D, BERNACKI, R. J
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Biological and medical sciences; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - metabolism; Cell Division - drug effects; Cell Survival - drug effects; Chemotherapy; Humans; Medical sciences; Mice; Mice, Nude; Pharmacology. Drug treatments; Putrescine - metabolism; Spermidine - metabolism; Spermine - analogs & derivatives; Spermine - metabolism; Spermine - pharmacokinetics; Spermine - therapeutic use; Spermine - toxicity; Tumor Cells, Cultured; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism
• ISSN: 1078-0432; 1557-3265

The spermine analogue N1,N11-diethylnorspermine (DENSPM) has been shown to induce the polyamine-acetylating enzyme spermidine/spermine N1-acetyltransferase, disrupt polyamine pool homeostasis, and inhibit tumor growth. DENSPM is currently being developed as an anti-neoplastic agent and is about to enter Phase II clinical trials. In this report, the antitumor efficacy of DENSPM was evaluated against a human transitional cell bladder BL13 carcinoma xenograft implanted orthotopically and s.c. in nude athymic mice. DENSPM was administered via continuous s.c. infusion at 93 mg/kg/day for 5 days. Treatment with DENSPM was well tolerated and produced tumor regressions in all mice with a significant proportion (up to 50%) of apparent cures. On the basis of low toxicity and good therapeutic efficacy, there is a strong rationale for evaluation of the therapeutic efficacy of DENSPM against bladder carcinomas in Phase II clinical trials.