The applicant proposes to study IP biochemical modulation of FUdR given with IP leucovorin and to determine its pharmacologic and clinical consequences. Fluoropyrimidine catabolic pathways as well as changes in the customary pharmacologic parameters will be measured. In addition, he will attempt to establish the pharmacodynamic effects of such modulation, and to evaluate portal versus systemic FUdR levels in selected patients. Such studies may impact on development of adjuvant therapies. Finally, an animal model will assist in studying pharmacologic consequences of IP FUdR + leucovorin further, and allow study of other forms of biochemical modulation or other modalities in combination.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050412-03
Application #
3194863
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1990-08-15
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1994-07-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Israel, V K; Jiang, C; Muggia, F M et al. (1995) Intraperitoneal 5-fluoro-2'-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study. Cancer Chemother Pharmacol 37:32-8
Muggia, F M; Tulpule, A; Retzios, A et al. (1994) Intraperitoneal 5-fluoro-2'-deoxyuridine with escalating doses of leucovorin: pharmacology and clinical tolerance. Invest New Drugs 12:197-206
Muggia, F M; Baranda, J (1993) Management of peritoneal carcinomatosis of unknown primary tumor site. Semin Oncol 20:268-72
Muggia, F M; LePoidevin, E; Jeffers, S et al. (1992) Intraperitoneal therapy for ovarian cancer: analysis of fluid distribution by computerized tomography. Ann Oncol 3:149-54
Muggia, F M; Chan, K K; Russell, C et al. (1991) Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2'-deoxyuridine. Cancer Chemother Pharmacol 28:241-50