Unusual central nervous system toxicity in a phase I study of N1 N11 diethylnorspermine in patients with advanced malignancy

Investigational New Drugs

Volumn 15, Issue 3, 1997, Pages 227-234

  Creaven, Patrick J ^a   Perez, Raymond ^a   Pendyala, Lakshmi ^a   Meropol, Neal J ^a   Loewen, Gregory ^a   Levine, Ellis ^a   Berghorn, Elmer ^a   Raghavan, Derek ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

CNS toxicity; Diethylnorspermine; Pharmacokinetics; Phase I

Indexed keywords

ACYLTRANSFERASE; ANTINEOPLASTIC AGENT; DIETHYLNORSPERMINE; POLYAMINE; SPERMINE DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; ADVANCED CANCER; AGED; ARTICLE; ATAXIA; BIOSYNTHESIS; CENTRAL NERVOUS SYSTEM; CLINICAL ARTICLE; CLINICAL TRIAL; DEGRADATION; DOSE RESPONSE; DYSARTHRIA; DYSPHAGIA; ENZYME INDUCTION; FEMALE; HEADACHE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HOT FLUSH; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; MUSCLE WEAKNESS; NAUSEA; NEUROTOXICITY; PARESTHESIA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; VERTIGO; VOMITING;

ADENOCARCINOMA; ADULT; AGED; ANTINEOPLASTIC AGENTS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CENTRAL NERVOUS SYSTEM DISEASES; COLONIC NEOPLASMS; FEMALE; HALF-LIFE; HUMANS; LUNG NEOPLASMS; MALE; MELANOMA; METABOLIC CLEARANCE RATE; MIDDLE AGED; NEOPLASMS; SPERMINE;

EID: 0030659113     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1005827231849     Document Type: Article

References (29)

1. Williams-Ashman HG, Canellakis ZN: Polyamines in mammalian biology and medicine. Perspect Biol Med 22: 421-453, 1979.
2. Pegg AE, McCann PP: Polyamine metabolism and function. Am J Physiol 243: C212-221, 1982.
3. Pegg AE: Polyamine metabolism and its importance in neoplastic growth and as a target for chemotherapy. Cancer Res 48: 759-774, 1988.
4. Pegg AE: Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J 234: 249-262, 1986.
5. Porter CW, Tabor H: Interference with polyamine biosynthesis and/or function by analogs of polyamines or methionine as a potential anticancer chemotherapeutic strategy. Anticancer Res 6: 525-542, 1986.
6. Porter CW, Janne J: Modulation of antineoplastic drug action by inhibitors of polyamine biosynthesis, in McCann PP, Pegg AE, Joerdsma AS (eds): Inhibition of Polyamine Metabolism: Biological Significance and Basis for New Therapies. Orlando, FL, Academic Press, Inc., 1987, pp 203-248.
7. Metcalf BW, Bey P, Danzin C, et al: Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C. 4.1.17) by substrate and product analogues. J Am Chem Soc 100: 2551-2553, 1978.
8. Abeloff MD, Slavik M, Luk GD, et al: Phase I trial and pharmacokinetic studies of a-difluoromethylornithine - an inhibitor of polyamine biosynthesis. J Clin Oncol 2: 124-130, 1984.
9. Maddox AM, Keating MJ, McCredie KE, et al: Phase I evaluation of intravenous difluoromethylornithine - a polyamine inhibitor. Invest New Drugs 3: 287-292, 1985.
10. Creaven PJ, Pendyala L, Petrelli NJ: Evaluation of a-difluoromethylornithine as a potential chemopreventive agent: tolerance to daily oral administration in humans. Cancer Epid Biomarkers & Prev 2: 243-247, 1993.
11. Love RR, Carbone PP, Verma AK, et al: Randomized phase I chemoprevention dose-seeking study of a-difluoromethylornithine. JNCI 85(9): 732-737, 1993.
12. Meyskens FLJr, Emerson SS, Pelot D, et al: Dose de-escalation chemoprevention trial of a-difluoromethylornithine in patients with colon polyps. JNCI 86(15): 1122-1130, 1994.
13. Pera PJ, Kramer DL, Sufrin JR, et al: Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines. Cancer Res 46: 1148-1154, 1986.
14. Pendyala L, Creaven PJ, Porter CW: Urinary and erythrocyte polyamines during the evaluation of oral a-difluoromethylornithine in a phase I chemoprevention clinical trial. Cancer Epid Biomarkers & Prev 2: 235-241, 1993.
15. Meyskens FL, Kingsley EM, Glattke T, et al: A phase II study of a-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. Invest New Drugs 4: 257-262, 1986.
16. Pera PJ, Kramer DL, Sufrin JR, et al: Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines. Cancer Res 46: 1148-1154, 1986.
17. Pendyala L, Creaven PJ, Porter CW: Urinary and erythrocyte polyamines during the evaluation of oral a-difluoromethylornithine in a phase I chemoprevention clinical trial. Cancer Epid Biomarkers & Prev 2: 235-241, 1993.
18. Meyskens FL, Kingsley EM, Glattke T, et al: A phase II study of a-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. Invest New Drugs 4: 257-262, 1986.
19. Abeloff MD, Rosen ST, Luk GD, et al: Phase II trials of a-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Cancer Treat Rep 70: 843-845, 1986.
20. Kelloff GJ, Boon CW, Steele VE, et al: Mechanistic considerations in chemopreventive drug development. J Cell Biochem Suppl 20: 1-24, 1994.
21. Kelloff GJ, Crowell JA, Boone CW, et al: Strategy and planning for chemopreventive drug development: clinical development plans. J Cell Biochem Suppl 20: 55-299, 1994.
22. Porter CW, Bergeron RJ: Enzyme regulation as an approach to interference with polyamine biosynthesis - an alternative to enzyme inhibition. In Weber G (ed), Advances in Enzyme Regulation. Pergamon Press New York and Oxford, 1988, Vol 27, pp 57-79.
23. 1-bis(ethyl)spermine homologues against human MALME-3 melanoma xenografts. Cancer Res 52: 2424-2430, 1992.
24. Kabra PM, Lee HK: Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography: improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr 380: 19-32, 1986.
25. Rocci ML Jr, Jusko WJ: LAGRAN program for area and moments in pharmacokinetic analysis. Comput Programs Biomed 16: 203-216, 1983.
26. Williams-Ashman HG, Schenone A: Methyl-glyoxal-bis (guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylases. Biochem Biophys Res Commun 46: 288-295, 1972.
27. Regelson W, Holland JF: Clinical experience with methylglyoxal-bis(guanylhydrazone) HCL (methyl-GAG), a new agent with clinical activity in acute myelocytic leukemia and the lymphomas. Cancer Chemother Rep 27: 15-26, 1963.
28. Mick R, Ratain MJ: Model-guided determination of maximum tolerated dose in phase I clinical trials: evidence for increased precision. JNCL 85(3): 217-223, 1993.
29. Ratain MJ, Mick R, Schilsky RL, et al: JNCI 85(20): 1637-1643, 1993 (commentary).