Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency

Cancer Chemotherapy and Pharmacology

Volumn 78, Issue 1, 2016, Pages 151-156

  Saif, Muhammad Wasif ^a   Diasio, Robert B ^b  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MAYO CLINIC   (United States)

Author keywords

5 Fluorouracil; DPYD gene; Fluoropyrimidines; PN401; Uridine

Indexed keywords

ANTIHISTAMINIC AGENT; CREATININE; DIHYDROPYRIMIDINE DEHYDROGENASE; FLUOROURACIL; GEMCITABINE; STEROID; URIDINE TRIACETATE; ACETIC ACID DERIVATIVE; ANTIDOTE; ANTINEOPLASTIC ANTIMETABOLITE; URIDINE;

ADULT; ADVANCED CANCER; AGED; ARTICLE; AUTOPSY; BLOOD CLOTTING DISORDER; CANCER CHEMOTHERAPY; CANCER PATIENT; CASE REPORT; CHEMOTHERAPY INDUCED ANEMIA; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; DRUG DOSE REDUCTION; DRUG FATALITY; DRUG MEGADOSE; DRUG WITHDRAWAL; ENZYME ACTIVITY; ERYTHROCYTE TRANSFUSION; FEMALE; GENE MUTATION; GENOTYPE; HETEROZYGOSITY; HOSPITAL ADMISSION; HUMAN; HUMAN TISSUE; MALE; MEDICAL HISTORY; MENTAL DETERIORATION; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROTOXICITY; OPEN STUDY; PANCREAS ADENOCARCINOMA; PANCYTOPENIA; PERIORBITAL EDEMA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; SIDE EFFECT; STEROID THERAPY; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; ANALOGS AND DERIVATIVES; COMPLICATION; PANCREATIC NEOPLASMS; SEVERITY OF ILLNESS INDEX; TIME FACTOR;

ACETATES; AGED; ANTIDOTES; ANTIMETABOLITES, ANTINEOPLASTIC; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; FEMALE; FLUOROURACIL; HUMANS; MALE; PANCREATIC NEOPLASMS; SEVERITY OF ILLNESS INDEX; TIME FACTORS; URIDINE;

EID: 84976329755     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-016-3063-1     Document Type: Article

References (31)

1. Allegra CJ, Grem JL (1997) Antimetabolites. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5th edn. 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. 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
5. Johnson MR, Diasio R (2001) Importance of dihydropyrimidine dehydrogenase (DYPD) deficiency in patients exhibiting toxicity following treatment with 5-fluorouracil. Adv Enzyme Regul 41:151–157
6. Van Kuilenburg AB, Haasjes J, Richel DJ, Zoetekouw L, Van Lenthe H, DeAbreu RA, Maring JG, Vreken P, Van Gennip AH (2000) Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity; identification of new mutations in the DPD gene. Clin Cancer Res 12:4705–4712
7. Diasio RB, Beavers TL, Carpenter JT (1988) Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Investig 81:47–51
8. Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB (1999) Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient following treatment with topical 5-fluorouracil. Clin Cancer Res 5:2006–2011
9. Martin DS, Stolfi RL, Sawyer RC, Spiegelman S, Young CW (1982) High-dose 5 fluorouracil with delayed “uridine” rescue in mice. Cancer Res 42:3964–3970
10. Klubes P, Cerna I, Meldon MA (1982) Uridine rescue from the lethal toxicity of 5-fluorouracil in mice. Cancer Chemother Pharmacol 8:17–21
11. Martin DS, Stolfi RL, Sawyer RC (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
12. Klubes P, Leyland-Jones B (1989) Enhancement of the antitumor activity of 5-fluorouracil by uridine rescue. Pharmacol Ther 41:289–302
13. 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. Pharmacol 43:2543–2549
14. Leyva A, van Groeningen CJ, Kraal I, Gall H, Peters GJ, Lankelma J, Pinedo HM (1984) Phase I and pharmacokinetic studies of high-dose uridine intended for rescue from 5-fluorouracil toxicity. Cancer Res 44:5928–5933
15. Van Groeningen CJ, Peters GJ, Nadal JC, Laurensse E, Pinedo HM (1991) Clinical and pharmacologic study of orally administered uridine. J Natl Cancer Inst 83:437–441
16. Kemeny N, Martin D, Schneider A, Williams L, Colofiore J, Sawyer R (1993) Uridine allows dose escalation of 5-fluorouracil when given with N-phosphonacetyl-l-aspartate, methotrexate, and leucovorin. Cancer 71:1875–1881
17. Schwartz GK, Christman K, Saltz L, Casper E, Quan V, Bertino J, Martin DS, Colofiore J, Kelsen D (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
18. Saif MW, von Borstel R (2005) 5-Fluorouracil dose escalation enabled with PN401 (triacetyluridine): toxicity reduction and increased antitumor activity in mice. Cancer Chemother Pharmacol 27:1–7
19. Kelsen DP, Martin D, O’Neil J, Schwartz G, Saltz L, Sung MT, von Borstel R, Bertino J (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
20. Bamat MK, Tremmel R, O’Neil JD et al (2010) Uridine triacetate: an orally administered, lifesaving antidote for 5-FU overdose [ASCO abstract 9084]. J Clin Oncol 28(suppl 15)
21. Von Borstel R, O’Neil JD, Saydoff JA, Bamat MK (2010) Uridine triacetate for lethal 5-FU toxicity due to dihydropyrimidine dehydrogenase (DPD) deficiency. J Clin Oncol 28(Suppl 15):e13505
22. Johnson MR, Yan J, Shao L, Albin N, Diasio RB (1997) Semi-automated radioassay for determination of dihydropyrimidine dehydrogenase (DPD) activity. Screening cancer patients for DPD deficiency, a condition associated with 5-fluorouracil toxicity. J Chromatogr B Biomed Sci Appl 696:183–191
23. Lu Z, Zhang R, Diasio RB (1993) Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res 53:5433–5438
24. Ezzeldin H, Okamoto Y, Johnson MR, Diasio RB (2002) A high-throughput denaturing high-performance liquid chromatography method for the identification of variant alleles associated with dihydropyrimidine dehydrogenase deficiency. Anal Biochem 306:63–73
25. Saif MW, Ezzeldin H, Vance K, Sellers S, Diasio RB (2007) DPYD*2A mutation: the most common mutation associated with DPD deficiency. Cancer Chemother Pharmacol 60(4):503–507
26. Ma WW, Saif WM, El-Rayes BF, Fakih M, Cartwright TH, Posey J, von Borstel R, Bamat MK (2016) Clinical trial experience with uridine triacetate for 5-fluorouracil toxicity. J Clin Oncol 34(Suppl 4S):655
27. Hildalgo 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
28. Ashour OM, Naguib FN, Panzica RP (2000) Al Safarjalani ON, el Kouni MH. 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 60:427–431
29. https://clinicaltrials.gov/ct2/show/results/NCT00024427
30. Harris BE, Song R, Soong SJ, Diasio RB (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
31. Saif MW (2013) Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU-and capecitabine-related toxicity using full sequencing of DPYD. Cancer Genom Proteom 10(2):89–92