Pharmacokinetic and pharmacodynamic effects of oral eniluracil, fluorouracil and leucovorin given on a weekly schedule

Cancer Chemotherapy and Pharmacology

Volumn 52, Issue 1, 2003, Pages 79-85

  Guo, Xiao Du ^a   Harold, Nancy ^a   Wasif Saif, M ^a   Schuler, Barbara ^a   Szabo, Eva ^a   Hamilton, J Michael ^a   Monahan, Brian P ^b   Quinn, Mary G ^a   Cliatt, Janet ^a   Nguyen, Diana ^a   Grollman, Frank ^a   Thomas, Rebecca R ^a   McQuigan, Elizabeth A ^b   Wilson, Richard ^a   Takimoto, Chis H ^a   Grem, Jean L ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b WALTER REED ARMY MEDICAL CENTER   (United States)

Author keywords

Dihydropyrimidine dehydrogenase; Eniluracil; Fluorouracil; Pharmacokinetics; Thymidylate synthase

Indexed keywords

5 ETHYNYLURACIL; DIHYDROPYRIMIDINE DEHYDROGENASE; DRUG METABOLITE; FLUORO BETA ALANINE; FLUOROURACIL; FOLINIC ACID; THYMIDYLATE SYNTHASE; UNCLASSIFIED DRUG; URACIL;

ABDOMINAL DISCOMFORT; ADULT; AGED; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; BLOOD TOXICITY; BONE MARROW; CANCER COMBINATION CHEMOTHERAPY; CELL ISOLATION; CLINICAL ARTICLE; CLINICAL PROTOCOL; COLORECTAL CANCER; COMPLEX FORMATION; CONFUSION; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DISEASE COURSE; DISEASE SEVERITY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE REGIMEN; DRUG EFFECT; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG INFUSION; DRUG URINE LEVEL; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; EYE DISEASE; FATIGUE; FEMALE; GAIT DISORDER; GRANULOCYTOPENIA; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MONONUCLEAR CELL; MUCOSA INFLAMMATION; NAUSEA AND VOMITING; NEUROTOXICITY; OUTCOMES RESEARCH; PARAMETER; PHARMACODYNAMICS; PHARMACOKINETICS; PLASMA CLEARANCE; POLYNEUROPATHY; PRIORITY JOURNAL; SENSORIMOTOR NEUROPATHY; SINGLE DRUG DOSE; SKIN DISEASE; THROMBOCYTOPENIA; URINARY EXCRETION;

ADMINISTRATION, ORAL; ADULT; AGED; ANTIMETABOLITES, ANTINEOPLASTIC; AREA UNDER CURVE; ENZYME INHIBITORS; FEMALE; FLUOROURACIL; HALF-LIFE; HUMANS; INFUSIONS, INTRAVENOUS; LEUCOVORIN; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; NEOPLASMS; URACIL;

EID: 0042671111     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-003-0613-0     Document Type: Article

References (27)

1. Baker SD, Khor SP, Adjei AA, Doucette M, Spector T, Donehower RC, Grochow LB, Sartorius SE, Noe DA, Hohneker JA, Rowinsky EK (1996) Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase. J Clin Oncol 14:3085
2. Baker SD, Diasio RB, O'Reilly S, Lucas VS, Khor SP, Sartorius SE, Donehower RC, Grochow LB, Spector T, Hohneker JA, Rowinsky EK (2000) Phase I and pharmacologic study of oral fluorouracil on a chronic daily schedule in combination with the dihydropyrimidine dehydrogenase inactivator eniluracil. J Clin Oncol 18:915
3. Bi D, Anderson LW, Shapiro J, Shapiro A, Grem JL, Takimoto CH (2000) Measurement of plasma uracil using gas chromatography-mass spectrometry in normal individuals and in patients receiving inhibitors of dihydropyrimidine dehydrogenase. J Chromatogr B Biomed Sci Appl 738:249
4. Chu E, Koeller DM, Casey JL, Drake JC, Chabner BA, Elwood PC, Zinn S, Allegra CJ (1991) Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase. Proc Natl Acad Sci U S A 88:8977
5. Chu E, Voeller DM, Jones KL, Takechi T, Maley GF, Maley F, Segal S, Allegra CJ (1994) Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells. Mol Cell Biol 14:207
6. Grem JL, Harold N, Keith B, Nguyen D, Zentko S, Takimoto CH, Shapiro J, Monahan BP, Hamilton JM, Quinn MG, Morrison G, Schuler B (2000) A phase I and pharmacodynamic trial of oral eniluracil, 5-fluorouracil and leucovorin on a weekly schedule. Proc ASCO 19:abstract 684
7. Grem JL, Harold N, Shapiro J, Bi DQ, Quinn MG, Zentko S, Keith B, Hamilton JM, Monahan BP, Donavan S, Grollman F, Morrison G, Takimoto CH (2000) Phase I and pharmacokinetic trial of weekly oral fluorouracil given with eniluracil and low-dose leucovorin to patients with solid tumors J Clin Oncol 18:3952
8. Heslin MJ, Yan J, Shao L, Weingarten J, Mangum SG, Ertel PJ, Lucas VS, Diasio RB (2000) Dihydropyrimidine dehydrogenase rapidly regenerates after inactivation by eniluracil (776C85) in primary and metastatic colorectal cancer. Proc ASCO 19:abstract 682
9. Johnston PG, Drake JC, Trepel J, Allegra CJ (1992) Immunological quantitation of thymidylate synthase using the monoclonal antibody TS106 in 5-fluorouracil-sensitive and -resistant human cancer cell lines. Cancer Res 52:4306
10. Keith B, Guo XD, Zentko S, Harold N, Schuler B, Quinn M, Shapiro J, Grem JL (2002) Impact of two weekly schedules of oral eniluracil given with fluorouracil and leucovorin on the duration of dihydropyrimidine dehydrogenase inhibition. Clin Cancer Res 8:1045
11. Kitchens ME, Forsthoefel AM, Rafique Z, Spencer HT, Berger FG (1999) Ligand-mediated induction of thymidylate synthase occurs by enzyme stabilization: implications for autoregulation of translation. J Biol Chem 274:12544
12. Knowling M, Browman G, Siu L, Khoo K, Cooke A, Tannock I, Klaassen D, Cripps C, Goss G, Matthews S, Clarke R, Seymour L (2001) A National Cancer Institute of Canada clinical trials group phase II study of eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous cell head and neck cancer. Ann Oncol 12:919
13. Levin J, Hohneker J (2000) Clinical development of eniluracil/fluorouracil: an oral treatment for patients with solid tumors. Invest New Drugs 18:383
14. Mani S, Hochster H, Beck T, Chevlen EM, O'Rourke MA, Weaver CH, Bell WN, White R, McGuirt C, Levin J, Hohneker J, Schilsky RL, Lokich J (2000) Multicenter phase II study to evaluate a 28-day regimen of oral fluorouracil plus eniluracil in the treatment of patients with previously untreated metastatic colorectal cancer. J Clin Oncol 18:2894
15. Marsh J, Catalano P, Huang J, Haberman D, Cornfeld MJ, O'Dwyer P, Benson AB III (2001) Phase II trial of oral fluorouracil (5-FU) plus oral eniluracil (GW776C85) administered over 28 days for patients with advanced colorectal cancer (E4296): a trial of the Eastern Cooperative Oncology Group (ECOG). Proc ASCO 20:abstract 547
16. Meropol NJ, Niedzwiecki D, Hollis D, Schilsky RL, Mayer RJ (2001) Phase II study of oral eniluracil 5-fluorouracil and leucovorin in patients with advanced colorectal carcinoma. Cancer 91:1256
17. Ochoa L, Hurwitz HI, Wilding G, Cohen D, Thomas JP, Schwartz G, Monroe P, Petros WP, Ertel VP, Hsieh A, Hoffman C, Drengler R, Magnum S, Rowinsky EK (2000) Pharmacokinetics and bioequivalence of a combined oral formulation of eniluracil an inactivator of dihydropyrimidine dehydrogenase and 5- fluorouracil in patients with advanced solid malignancies. Ann Oncol 11:1313
18. Paff MT, Baccanari DP, Davis ST, Cao S, Tansik RL, Rustum YM, Spector T (2000) Preclinical development of eniluracil: enhancing the therapeutic index and dosing convenience of 5-fluorouracil. Invest New Drugs 18:365
19. Ren Q-F, Kao V, Grem J (1998) Cytotoxicity and DNA fragmentation associated with sequential gemcitabine and 5-fluoro2′-deoxyuridine in HT29 colon cancer cells. Clin Cancer Res 4:2811
20. Rivera E, Sutton L, Colwell B, Graham M, Frye D, Somerville M, Conklin HS, McGuirt C, Levin J, Hortobagyi GN (2002) Multicenter phase II study of a 28-day regimen of orally administered eniluracil and fluorouracil in the treatment of patients with anthracycline- and taxane-resistant advanced breast cancer. J Clin Oncol 20:987
21. Saif MW, Wilson RH, Harold N, Keith B, Dougherty DS, Grem JL (2001) Peripheral neuropathy associated with weekly oral 5-fluorouracil leucovorin and eniluracil. Anticancer Drugs 12:525
22. Schilsky RL, Hohneker J, Ratain MJ, Janisch L, Smetzer L, Lucas VS, Khor SP, Diasio R, Von Hoff DD, Burris HA 3rd (1998) Phase I clinical and pharmacologic study of eniluracil plus fluorouracil in patients with advanced cancer. J Clin Oncol 16:1450
23. Schilsky RL, Bukowski R, Burris H 3rd, Hochster H, O'Rourke M, Wall JG, Mani S, Bonny T, Levin J, Hohneker JA (2000) A multicenter phase II study of a five-day regimen of oral 5-fluorouracil plus eniluracil with or without leucovorin in patients with metastatic colorectal cancer. Ann Oncol 11:415
24. Schilsky RL, Levin J, West WH, Wong A, Colwell B, Thirlwell MP, Ansari RH, Bell WN, White RL, Yates BB, McGuirt PV, Pazdur R (2002) Randomized open-label phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer. J Clin Oncol 20:1519
25. Skovsgaard T, Davidson NG, Piccart MJ, Richel DJ, Bonneterre J, Cirkel DT, Barton CM (2001) A phase II study of oral eniluracil/fluorouracil in patients with anthracycline-refractory or anthracycline- and taxane-refractory advanced breast cancer. Ann Oncol 12:1255
26. Smith IE, Johnston SR, O'Brien ME, Hickish TF, de Boer RH, Norton A, Cirkel DT, Barton CM (2000) Low-dose oral fluorouracil with eniluracil as first-line chemotherapy against advanced breast cancer: a phase II study. J Clin Oncol 18:2378
27. Van Cutsem E, Sorensen J, Cassidy J, Daniel F, Harper P, Bailey N, Peachey M, Somerville M (2001) International phase III study of oral eniluracil plus 5-fluorouracil versus intravenous 5-FU plus leucovorin in the treatment of advanced colorectal cancer. Proc ASCO 20:abstract 522