Robert B. Diasio, MD | Authors

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Articles

Current Status of Oral Chemotherapy for Colorectal Cancer

March 02, 2001

The treatment of advanced colorectal cancer over the past 4 decades has required the use of intravenous chemotherapy, most typically fluorouracil (5-FU). The possibility of providing

Clinical Implications of Dihydropyrimidine Dehydrogenase on 5-FU Pharmacology

January 02, 2001

Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU), accounting for catabolism of over 85% of an administered dose of 5-FU. DPD plays an important role in

Oral DPD-Inhibitory Fluoropyrimidine Drugs

October 01, 2000

Over the past decade, increasing data have emphasized both the importance of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in the catabolism of fluorouracil (5-FU), and its role as a control step in 5-FU metabolism, regulating the availability of 5-FU for anabolism.

The Role of Dihydropyrimidine Dehydrogenase (DPD) Modulation in 5-FU Pharmacology

October 01, 1998

Over the past several years, the pyrimidine catabolic pathway and, in particular, the first enzymatic step involving dihydropyrimidine dehydrogenase (DPD) have been recognized as being critical in determining the ultimate

Improving 5-FU With A Novel Dihydropyrimidine Dehydrogenase Inactivator

March 01, 1998

GW776C85 is a new drug that has been shown to be an effective inactivator of dihydropyrimidine dehydrogenase (DPD). Preclinical studies demonstrated that administration of GW776C85 with 5-fluorouracil (5-FU) resulted in several desirable pharmacologic effects. Initial clinical data on 5-FU combined with GW776C85 suggest potentially increased antitumor activity in at least some malignancies with tolerable toxicity, as well as several distinct economic and quality-of-life advantages including the following: (1) The possibility of administering 5-FU as an oral drug due to excellent bioavailability of 5-FU following inactivation of DPD; (2) a cost-effective alternative to continuous or protracted infusion of 5-FU without the need for hospitalization or surgical placement of an intravenous access and availability of an ambulatory pump; and (3) potential for less interpatient variation of 5-FU toxicity (eg, in host tissues, such as bone marrow and gastrointestinal mucosa cells) due to inactivation of DPD in essentially all patients treated, permitting better 5-FU dosing guidelines. Finally, because tumors may theoretically become resistant to 5-FU by increased levels of DPD, the use of GW776C85 to inactivate DPD may provide a potential means by which tumor resistance can be reversed. [ONCOLOGY(Suppl 4):51-56, 1998]

Clinical Implications of Dihydropyrimidine Dehydrogenase Inhibition

July 01, 1997

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD has an important role in regulating the availability of 5-FU for anabolism. It is now clear that DPD also