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Leucovorin modulation of fluorouracil
L Grogan1, G A Sotos, C J Allegra
1NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Oncology (Williston Park, N.Y.)
|August 1, 1993
Summary
Leucovorin enhances fluorouracil
Area of Science:
- Oncology
- Pharmacology
Background:
- Fluorouracil is a key chemotherapy for colorectal cancer.
- Its action involves inhibiting thymidylate synthase (TS).
Purpose of the Study:
- To evaluate leucovorin's role in enhancing fluorouracil efficacy.
- To determine optimal leucovorin dosing and scheduling for colorectal cancer treatment.
Main Methods:
- Review of preclinical studies and clinical trials on fluorouracil and leucovorin.
- Analysis of various drug doses and administration schedules.
Main Results:
- Continuous infusion or low-dose leucovorin schedules are effective.
- These schedules maximize intracellular polyglutamated 5,10-methylenetetrahydrofolate levels.
- Optimal efficacy is less dependent on leucovorin dose with these schedules.
Conclusions:
- Continuous or repetitive low-dose leucovorin enhances fluorouracil's anti-cancer activity.
- Optimized folate metabolism through leucovorin improves TS inhibition.
- These strategies offer effective colorectal cancer chemotherapy.