Drug type
• A pyrimidine antagonist
• Classified as an antimetabolite antineoplastic agent
Indications
• Colorectal cancer
• Gastric cancer
• Metastatic breast carcinoma
• Metastatic colorectal cancer
• Pancreatic carcinoma
• Fluorouracil is also used when surgery or irradiation is not feasible for the palliative treatment of the following carcinomas
—Breast
—Stomach
—Pancreas
—Colon
—Rectum
Unlabeled uses
• Biliary tract malignancy
• Carcinoid syndrome
• Localized malignant tumor of anus
• Locally advanced breast carcinoma
• Malignant esophagus neoplasm
• Malignant tumor of cervix
• Malignant tumor of head and neck
• Malignant tumor of urinary bladder
• Metastatic malignant tumor of anus
• Combination therapies for colorectal cancer
—Fluorouracil is designated an orphan drug by the FDA for use in combination with leucovorin for the treatment of metastatic adenocarcinoma of the colon and rectum.
Mechanism of action
• Main mechanism thought to be the binding of deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5-10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex, which inhibits the formation of thymidylate from uracil
—Interferes with DNA synthesis
• Also, fluorouracil triphosphate (FUTP) can be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA
—Interferes with RNA processing and protein synthesis
Dosage and administration
• Fluorouracil is administered intravenously.
• Care should be taken to avoid extravasation of the drug.
• Adult dose
—Minimum: 346.0 mg/1.73 m2
—Maximum: 865.0 mg/1.73 m2
• Pediatric dose
—Minimum: 346.0 mg/1.73 m2
—Maximum: 865.0 mg/1.73 m2
Pregnancy and lactation
• Pregnancy category D
—Fluorouracil may cause fetal harm when administered to a pregnant woman.
• Lactation
—Absolute contraindication
Cautions and adverse effects
• Toxicity depends on route and duration of treatment
• Adverse effects
—Most frequent:
• Dermatologic: Allergic dermatitis, palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome), pruritus of skin, skin rash
• Heme: Infection, leukopenia
• Gastroinestinal: Anorexia, aphthous stomatitis, diarrhea, heartburn, nausea, vomiting
• Others: Allergic reactions, alopecia, fatigue, general weakness
—Less frequent:
• Dry skin
• Gastrointestinal ulcer
• Thrombocytopenic disorder
—Rare:
• CNS: Acute cerebellar syndrome, ataxia, euphoria, headache disorder, impaired cognition, nystagmus
• Others: Myocardial ischemia, pulmonary disease, sensation disturbance of limbs