5-Fluorouracil is indicated alone or in combination for carcinoma of the colon or rectum, carcinoma of the stomach and exocrine pancreas, carcinoma of the liver, carcinoma of the breast (an especially aggressive form of breast cancer), carcinoma of the bladder, carcinoma of the lung, epithelial ovarian carcinoma andcervical carcinoma.
Fluorouracil is inactive as such in mammalian cells but is converted into the active 5-fluorodeoxyuridine monophosphate (FdUMP) by a variety of different metabolic pathways. The drug works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus of DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. Fluorouracil as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.
Various protocols exist- 500 mg/m2 IV on Days 1-5, OR 450-600 mg/m2 IV weekly, OR 200-400 mg/m2 IV continuous infusion qD Not to exceed 800 mg/day The commonest schedules being 500 mg/m2 daily for 5 days repeated at 4-weekly intervals. Intravenous 5-FU can be delivered by rapid intravenous bolus injection or slow infusion. The vial contents can rapidly be injected directly into a peripheral vein. Slow intravenous infusion requires the drug to be diluted in 500 mL of dextrose 5% solution, then infused over 2-3 hours on 5 successive days.
Pre-treatment with cimetidine for 4 weeks led to increased plasma concentrations of fluorouracil following intravenous and oral administration in 6 patients. The effect was probably due to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.
It is contraindicated in patients that are severely debilitated or in patients with bone marrow suppression due to either radiotherapy or chemotherapy. It is likewise contraindicated in pregnant or breastfeeding women. It should also be avoided in patients that do not have malignant illnesses. Dose should be reduced in patients with compromised liver function. For intra-arterial infusion, 5000 U of L.M. heparin should be added to 1 L of 5% dextrose in water together with the daily dose of fluorouracil. Ulcer-like pain or other significant gastrointestinal symptoms are indications to discontinue intra-arterial therapy, as hemorrhage or perforation may occur. Precipitation may occur when leucovorin and fluorouracil are mixed in the same bag.
Mild to moderate cardiac effects, hepatic effects, hematological effects, neurological effects, allergic reaction, decreased bone marrow function, hand-foot syndrome, severe vomiting, diarrhoea, frequent bowel movements or watery stools, sores in the mouth or throat may occur.
Pregnancy category D. There are no data on the excretion of fluorouracil into human milk. Because fluorouracil inhibits DNA, RNA and protein synthesis, mothers should not nurse while receiving this drug.
Cases of deliberate overdose are unknown but excessive toxicity because of the hematological effects as described above. There is no specific antidote to 5-fluorouracil toxicity; treatment consists in supportive care. In addition to the hematological toxicity other toxicities will occur with overdose. Sign and symptoms are qualitatively similar to the side effects. Treatment should be performed promptly and appropriate drugs are given to control symptoms of overdose.
Store the vial in original carton not exceeding 25℃. Do not refrigerate. Protect from light.
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