5-Fluorouracil dose escalation enabled with PN401 (triacetyluridine): Toxicity reduction and increased antitumor activity in mice

Cancer Chemotherapy and Pharmacology

Volumn 58, Issue 1, 2006, Pages 136-142

  Saif, Muhammad Wasif ^a,c   Von Borstel, Reid ^b  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b Wellstat Therapeutics Corporation   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

5 Fluorouracil; DPD; Fluoropyrimidines; PN401; Uridine

Indexed keywords

5 ETHYNYLURACIL; ANTIDOTE; FLUOROURACIL; FOLINIC ACID; PRODRUG; TRIACETYLURIDINE; UNCLASSIFIED DRUG; URIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER INHIBITION; COLON ADENOCARCINOMA; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG OVERDOSE; DRUG SAFETY; FEMALE; LETHALITY; MAXIMUM TOLERATED DOSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SURVIVAL; TREATMENT OUTCOME;

ADENOCARCINOMA; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COLONIC NEOPLASMS; FEMALE; FLUOROURACIL; HUMANS; LEUCOVORIN; MAXIMUM TOLERATED DOSE; MICE; MICE, INBRED BALB C; SURVIVAL RATE; TUMOR BURDEN; URIDINE; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 33645981893     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-005-0129-x     Document Type: Article

References (24)

1. Allegra CJ, Grem JL (1997) Antimetabolites. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5. Lippincott-Raven, Philadelphia, pp 432-451
2. Sobrero AF, Aschele C, Bertino JR (1997) Fluorouracil in colorectal cancer: a tale of two drugs - implications for biochemical modulation. J Clin Oncol 15:368-381
3. Grem JL (1996) 5-Fluoropyrimidines. In: Chabner BA, Longo DL (eds) Cancer chemotherapy and biotherapy: principles and practice. Lippincott-Raven, Philadelphia, pp 149-211
4. Martin DS, Stolfi RL, Sawyer RC et al (1982) High-dose 5 fluorouracil with delayed "uridine" rescue in mice. Cancer Res 42:3964-3970
5. Klubes P, Cerna I, Meldon MA (1982) Uridine rescue from the lethal toxicity of 5-fluorouracil in mice. Cancer Chemother Pharmacol 8:17-21
6. Martin DS, Stolfi RL, Sawyer RC et al (1989) Use of oral uridine as a substitute for parenteral uridine rescue of 5-fluorouracil therapy, with and without the uridine phosphorylase inhibitor 5-benzylacyclouridine. Cancer Chemother Pharmacol 24:9-14
7. Klubes P, Leyland-Jones B (1989) Enhancement of the antitumor activity of 5-fluorouracil by uridine rescue. Pharmacol Ther 41:289-302
8. Nord LD, Stolfi RL, Martin DS (1992) Biochemical modulation of 5-fluorouracil with leucovorin or delayed uridine rescue: correlation of antitumor activity with dosage and FUra incorporation into RNA. Pharmacology 43:2543-2549
9. Leyva A, van Groeningen CJ, Kraal I et al (1984) Phase I and pharmacokinetic studies of high-dose uridine intended for rescue from 5-fluorouracil toxicity. Cancer Res 44:5928-5933
10. van Groeningen CJ, Peters GJ, Nodal JC et al (1991) Clinical and pharmacologic study of orally administered uridine. J Natl Cancer Inst 83:437-441
11. Seiter K, Kemeny N, Martin D et al (1993) Uridine allows dose escalation of 5-fluorouracil when given with N-phosphonacetyl-L-aspartate, methotrexate, and leucovorin. Cancer 71:1875-1881
12. Schwartz GK, Christman K, Saltz L et al (1996) A phase I trial of a modified, intensive FAMTX regimen (high dose 5-fluorouracil + doxorubicin + high dose methotrexate + leucovorin) with oral uridine rescue. Cancer 78:1988-1995
13. Kelsen DP, Martin D, O'Neil J et al (1997) Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer. J Clin Oncol 15:1511-1517
14. Codacci-Pisanelli G, Van der Wilt CL, Smid K, Noordhuis P, Voorn D, Pinedo HM, Peters GJ (2002) High-dose 5-fluorouracil with uridine-diphosphoglucose rescue increases thymidylate synthase inhibition but not 5-fluorouracil incorporation into RNA in murine tumors. Oncology 62(4):363-370
15. Ashour OM, Naguib FN, Panzica RP, Al Safarjalani ON, el Kouni MH (2000) Modulation of 5-fluorouracil host toxicity by 5-(benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-tri-O-acetyluridine, a prodrug of uridine. Biochem Pharmacol 60(3):427-431
16. Peters GJ, van Dijk J, van Groeningen CJ et al (1988) In vitro biochemical and in vivo biological studies of the uridine rescue of 5-fluorouracil. Br J Cancer 57:259-265
17. Inaba M, Mitsuhashi J, Ozawa S (1990) Kinetic analysis of 5-fluorouracil action against various cancer cells. Jpn J Cancer Res 81:1039-1044
18. Harris BE, Song R, Soong S et al (1990) Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res 50:197-201
19. Hryniuk WM, Figueredo A, Goodyear M (1987) Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. Semin Oncol 14(Suppl 4):3-11
20. Hidalgo M, Villalona-Calero MA, Eckhardt SG, Drengler RL, Rodriguez G, Hammond LA, Diab SG, Weiss G, Garner AM, Campbell E, Davidson K, Louie A, O'Neil JD, von Borstel R, Von Hoff DD, Rowinsky EK (2000) Phase I and pharmacologic study of PN401 and fluorouracil in patients with advanced solid malignancies. J Clin Oncol 18(1):167-177
21. Larsson A, Carlsson G, Gustavsson B et al (1996) Different intravenous administration techniques for 5-fluorouracil: pharmacokinetics and pharmacodynamic effects. Acta Oncol 35:207-212
22. McDermott BJ, van der Berg HW, Murphy RF (1982) Nonlinear pharmacokinetics for the elimination of 5-fluorouracil after intravenous administration in cancer patients. Chemother Pharmacol 9:173-178
23. Baker S (2000) Pharmacology of fluorinated pyrimidines: eniluracil. Invest New Drugs 18(4):373-381
24. Ezzeldin H, Diasio R (2004) Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. Clin Colorectal Cancer 4:181-189