5-Fluorouracil (5-FU)

5-Fluorouracil (5-FU) is an antimetabolite chemotherapy drug that is inactive in mammalian cells but is converted into active 5-fluorodeoxyuridine monophosphate (FdUMP) through various 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.

5-Fluorouracil as FdUMP is also incorporated into RNA, resulting in fluorination of RNA. The effect on living cells is limited mainly to those in the proliferative phase, though cells in G2 and S phase are most affected.

• Carcinoma of the colon or rectum
• Carcinoma of the stomach and exocrine pancreas
• Carcinoma of the liver
• Carcinoma of the breast
• Carcinoma of the bladder
• Carcinoma of the lung
• Epithelial ovarian carcinoma
• Cervical carcinoma
• Superficial basal cell carcinoma
• Esophageal carcinoma

Adults:
IV Palliation (Malignant neoplasms): 12 mg/kg/day (max 0.8-1 g/day) for 3-4 days; if no toxicity, after 1 day, 6 mg/kg on alternate days for 3-4 doses. Repeat course after 4-6 weeks or maintenance doses of 5-15 mg/kg (max 1 g) weekly.

Colon, Breast, Ovary, Liver, Pancreas, Rectum, Stomach Cancer: 500 mg/m² IV on Days 1-5; OR 450-600 mg/m² weekly; OR 200-400 mg/m² continuous IV infusion (max 800 mg/day). Infusion: 15 mg/kg/day (max 1 g/day) until toxicity or total 12-15 g given.

Intra-arterial: 5-7.5 mg/kg/day as continuous infusion (regional perfusion).

Cervical cancer (with cisplatin): 1 g/m² IV on day 1; repeat every 21 days.

Poor risk and malnourished patients: 6 mg/kg/day for 3 days (max 400 mg/day); if no toxicity, 3 mg/kg on days 5,7,9.

Hepatic & Renal impairment: Dose reduction may be required.

Children: Safety and efficacy not established.

Common side effects:
Increased risk of infection, mouth ulcer (stomatitis), vomiting, weakness, nausea, loss of appetite, hair loss, blisters on fingers/feet, decreased blood cells (RBC, WBC, platelets), diarrhea.

Hematological: Thrombocytopenia, leukopenia, anemia (may occur within first 10 days, resolves within 3 weeks).

Cardiac: Ischemic cardiac events (rare, may occur within hours of first dose).

Neurological: Cerebral ataxia (3.1-7%), acute cerebellar syndromes, myelopathy (intrathecal administration), conjunctivitis, tear duct stenosis, ectropion.

Hand-foot syndrome: Tingling, pain, redness, swelling or tenderness of hands and feet.

Allergic reactions: Difficulty breathing, swelling of lips/tongue/face, hives.

• 5-Fluorouracil is a highly toxic drug with a narrow margin of safety; therapeutic response is unlikely without some evidence of toxicity.
• Daily dose should not exceed 1 gram.
• Discontinue promptly when signs of toxicity appear: Leukopenia (WBC <3500/mm³), Thrombocytopenia (platelets <100,000/mm³), Stomatitis (first small ulceration at inner margin of lips), Severe diarrhea, GI ulceration and bleeding.
• May cause nausea, dizziness, and visual changes; do not drive until you know how it affects you.
• Do not use during pregnancy and lactation.
• Regular blood tests (CBC) and liver function monitoring are required.

• Severely debilitated patients
• Bone marrow suppression due to radiotherapy or chemotherapy
• Topical application on mucous membranes
• Exposure to sunlight
• Hypersensitivity
• Poor nutritional status
• Potentially serious infections
• Pregnancy and lactation
• Patients without malignant illness

• Warfarin: May increase warfarin effects.
• Vaccines: May reduce response to vaccines; possibility of generalized infection with live vaccines.
• Allopurinol: Action may be modified.
• Leucovorin calcium: May enhance toxicity of fluorouracil.
• Cimetidine: May increase plasma concentrations (due to hepatic enzyme inhibition and reduced hepatic blood flow).