Phase I clinical and pharmacologic study of Eniluracil plus fluorouracil in patients with advanced cancer

Journal of Clinical Oncology

Volumn 16, Issue 4, 1998, Pages 1450-1457

  Schilsky, Richard L ^a   Hohneker, John ^a   Ratain, Mark J ^a   Janisch, Linda ^a   Smetzer, Leslie ^a   Lucas, Virgil Sol ^a   Khor, Soo Peang ^a   Diasio, Robert ^a   Von Hoff, Daniel D ^a   Burris III, Howard A ^a  

^a University of Chicago   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 ETHYNYLURACIL; FLUOROURACIL; FOLINIC ACID;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; ARTICLE; BLOOD TOXICITY; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; DOSE RESPONSE; DRUG HALF LIFE; DRUG SAFETY; FEMALE; GASTROINTESTINAL TOXICITY; HAIR LOSS; HUMAN; HUMAN CELL; INTRAVENOUS DRUG ADMINISTRATION; MAJOR CLINICAL STUDY; MALE; MAXIMUM ALLOWABLE CONCENTRATION; NAUSEA; ORAL DRUG ADMINISTRATION; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SOLID TUMOR; VOMITING;

EID: 0031900670     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.1998.16.4.1450     Document Type: Article

References (23)

1. Sotos GA, Allegra CJ: Biochemical modulation of cancer chemotherapy, in Schilsky RL, Milano G, Ratain MJ (eds): Principles of Antineoplastic Drug Development and Pharmacology. New York, NY, Dekker, 1996, pp 143-187
2. Piedbois P, Buyse M, Rustum Y, et al: Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. J Clin Oncol 10:896-903, 1992
3. Advanced Colorectal Cancer Meta-Analysis Project: Metaanalysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. J Clin Oncol 12:960-969, 1994
4. Leichman CG, Fleming TR, Muggia FM, et al: Phase II study of fluorouracil and its modulation in advanced colorectal cancer: A Southwest Oncology Group Study. J Clin Oncol 13:1303-1311, 1995
5. Rougier P, Buyse M, Ryan L, et al: Meta-analysis of all trials comparing intravenous bolus administration to continuous infusion of 5-fluorouracil in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol 16:267A, 1997 (abstr)
6. Naguib FNM, El-Kouni MH, Sha S: Enzymes of uracil catabolism in normal and neoplastic human tissues. Cancer Res 45:5402-5412, 1985
7. Etienne MC, Cheradame S, Fischel JL, et al: Response to fluorouracil therapy in cancer patients: The role of tumoral dihydropyrimidine dehydrogenase activity. J Clin Oncol 13:1663-1670, 1995
8. Spector T, Harrington JA, Porter DJ: 5-Ethynyluracil (776C85): Inactivation of dihydropyrimidine dehydrogenase in vivo. Biochem Pharmacol 46:2243-2248, 1993
9. Porter DJT, Chestnut WG, Merrill BM, et al: Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil. J Biol Chem 267:5236-5242, 1992
10. Baccanari DP, Davis ST, Knick VC, et al: 776C85: Effects on the pharmacokinetics and antitumor activity of 5-fluorouradl. Proc Natl Acad Sci. USA 90:11064-11068, 1993
11. Cao S, Rustum YM, Spector T: 5-Ethynyluracil (776C85): Modulation of 5-fluorouracil efficacy and therapeutic index in rats bearing advanced colorectal carcinoma. Cancer Res 54:1507-1510, 1994
12. Spector T, Cao S, Rustum YM, et al: Attenuation of the antitumor activity of 5-fluorouracil by (R)-5-fluoro-5,6-dihydrouracil. Cancer Res 55:1239-1241, 1995
13. Fischel JL, Etienne MC, Spector T, et al: Dihydropyrimidine dehydrogenase: A tumoral target for fluorouracil modulation. Clin Cancer Res 1:991-996, 1995
14. Fischel JL, Formento P, Etienne et al: Dual modulation of 5-fluorouracil cytotoxicity using folinic acid with a dihydropyrimidine dehydrogenase inhibitor. Biochem Pharmacol 53:1703-1709, 1997
15. Baker SD, Khor SP, Adjei AA, et al: Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase. J Clin Oncol 14:3085-3096, 1996
16. Baker SD, Diasio R, Lucas VS, et al: Phase I and pharmacologic study of oral 5-fluorouracil on a chronic 28-day schedule in combination with the dihydropyrimidine dehydrogenase inactivator 776C85. Proc Am Soc Clin Oncol 15:486, 1996 (abstr)
17. Lu Z, Zhang R, Diasio RB: 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, 1993
18. Czejka MJ, Jager W, Schuller J, et al: Clinical pharmacokinetics of 5-fluorouracil. Influence of the biomodulating agents interferon, dipyridamole, and folinic acid alone and in combination. Arzneimittelforschung 43:387-390, 1993
19. Khor SP, Lucas S, Hsieh AY, et al: 776C85: Effect on renal elimination of 5-fluorouracil and uracil in cancer patients. Proc Am Assoc Cancer Res 37:371, 1996 (abstr)
20. Schilsky RL, Burris H, Ratain M, et al: Phase I clinical and pharmacologic study of 776C85 plus 5-fluorouracil in patients with advanced cancer. Proc Am Soc Clin Oncol 15:485, 1996 (abstr)
21. Grem JL: 5-Fluoropyrimidines, in Chabner BA, Longo DL (eds): Cancer Chemotherapy and Biotherapy: Principles and Practice (ed 2) Philadelphia, PA, Lippincott Raven, 1996, pp 149-217
22. Milano G, Etienne MC, Renee N, et al: Relationship between fluorouracil systemic exposure and tumor response and patient survival. J Clin Oncol 12:1291-1295, 1994
23. Schilsky R, Bukowski R, Burris H, et al: A phase II study of a five-day regimen of oral 5-fluorouracil plus 776C85 with or without leucovorin in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 16:271A, 1997 (abstr)