FLUOROURACIL 
Pronounciation
- (flew-roh-YOUR-ah-sill)
Trade Name(s)
- Adrucil, 5-Fluorouracil, 5-FU
Verify pregnancy status. Baseline studies indicated; see Monitor.
Many dosing regimens are in use. May be given as an injection or as a continuous infusion. Manufacturer recommends 12 mg/kg of body weight/24 hr for 4 days. Total dose should not exceed 800 mg/24 hr. If no toxicity is observed, one-half dose (6 mg/kg) is given on Days 6, 8, 10, and 12 unless toxicity occurs. No medication is given on Days 5, 7, 9, or 11. Discontinue therapy on Day 12, even if no toxicity is apparent. See Precautions/Monitor. The most common form of maintenance therapy is to repeat the entire course of therapy beginning 30 days after the previous course is completed and any toxicity has subsided or to give a single dose of 10 to 15 mg/kg/week, not to exceed 1 Gm/week. Dose adjustments of subsequent doses are made depending on side effects and tolerance.
Advanced colorectal cancer (unlabeled dose):
Various protocols have been used. Examples are leucovorin calcium 20 mg/M2 followed by fluorouracil 425 mg/M2, or leucovorin calcium 200 mg/M2 followed by fluorouracil 370 mg/M2 daily for 5 days. Repeat at 4-week intervals twice, then repeat every 28 to 35 days based on complete recovery from toxic effects. Do not initiate or continue in any patient with GI toxicity until completely subsided. Reduce fluorouracil dose based on tolerance to previous course; reduce 20% for moderate hematologic or GI toxicity, 30% for severe toxicity. Increase fluorouracil dose 10% if no toxicity. Leucovorin calcium dose is not adjusted. Alternatively, fluorouracil may also be used in combination with levoleucovorin; dose is different; see levoleucovorin monograph. Fluorouracil and leucovorin calcium are also used in combination with irinotecan (Camptosar); see irinotecan monograph.
Breast cancer (unlabeled dose):
Various protocols have been used. An example is fluorouracil 600 mg/M2 on Days 1 and 8 of each cycle combined with cyclophosphamide (Cytoxan) 100 mg/M2 on Days 1 through 14 of each cycle and methotrexate 40 mg/M2 on Days 1 and 8 of each cycle. Repeat cycles monthly (allowing a 2-week rest between cycles). Repeat for 6 to 12 cycles (6 to 12 months). Doxorubicin (Adriamycin) has also been included in this regimen. In patients older than 60 years of age, reduce the fluorouracil dose to 400 mg/M2 and the initial methotrexate dose to 30 mg/M2.
For poor-risk patients or those in a poor nutritional state, either reduce dose by one-half or more throughout a course of therapy or give 6 mg/kg/day for 3 days. If no toxicity observed, give 3 mg/kg on Days 5, 7, and 9. Give nothing on Days 4, 6, or 8. Do not exceed 400 mg/day. ■ Dose based on ideal body weight in presence of edema, ascites, or obesity. ■ Reduce dose in patients who have received high-dose pelvic irradiation or other cytotoxic drug therapy with alkylating agents (e.g., cisplatin, ifosfamide). ■ One source recommends a dose adjustment in patients with impaired hepatic function. Give the full dose if the bilirubin is 5 or less on the day of administration; omit the dose if the bilirubin is greater than 5. ■ Used with other antineoplastic drugs in reduced doses to achieve tumor remission. ■ See Usual Dose.
Specific techniques required; seePrecautions. May be slightly discolored without affecting safety and potency. Dissolve any precipitate by heating to 60° C (140° F) and shaking vigorously. Let cool to body temperature before using.
May be given undiluted. May inject through Y-tube or three-way stopcock of a free-flowing infusion.
May be further diluted with D5W or NS and given as an infusion. Doses up to 2 Gm are being given with extreme caution under the specific supervision of experienced specialists. Leucovorin calcium has been mixed into the solution with fluorouracil.
Store at room temperature; protect from light.
Compatibility information not available from manufacturer. Other sources suggest a few specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
A single dose over 1 to 15 minutes.
A single dose is usually administered over 24 hours. Toxicity may be lessened by extended administration.
An antimetabolite. A fluorinated pyrimidine antagonist, cell cycle specific, that interferes with the synthesis of DNA and RNA. Through various chemical processes this deprivation acts more quickly on rapidly growing cells and causes their death. Distributes into tumors, intestinal mucosa, bone marrow, liver, and readily crosses the blood-brain barrier into cerebrospinal fluid and brain tissue. Metabolized by the liver within 3 hours. Half-life is approximately 16 minutes. Excretion is through the urine and as respiratory CO2.
To suppress or slow neoplastic growth. Palliative treatment of cancers of the breast, colon, pancreas, rectum, and stomach. May be used alone or in combination with other agents.
Has been used for the treatment of bladder, cervical, endometrial, esophageal, head and neck, ovarian, prostatic, skin (topical), and other cancers. Consult oncology literature for protocols in use.
Potentially serious infections, depressed bone marrow function, poor nutritional state, hypersensitivity, major surgery within the previous month.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Administered by or under the direction of the physician specialist with facilities for monitoring the patient and responding to any medical emergency. Hospitalization, at least during the initial course of therapy, is recommended.■ Use caution in patients who have had high-dose pelvic irradiation, previous alkylating agents (e.g., cisplatin), other antimetabolic drugs (e.g., methotrexate), metastatic tumor involvement of the bone marrow, impaired hepatic or renal function, or dihydropyrimidine dehydrogenase deficiency. ■ Pseudomembranous colitis has been reported. May range from mild to life threatening. Consider in patients who present with diarrhea during or after treatment with fluorouracil.
Confirm patency of vein. Avoid extravasation. Change peripheral injection site every 48 hours. ■ Obtain a CBC with differential and platelet count before each dose. When given with leucovorin calcium, repeat weekly the first two courses and then at the time of anticipated WBC nadir in following courses. Electrolytes and liver function tests should be done before the first three courses, then every other course. ■ Be alert for signs of bone marrow suppression or infection. Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Examine mouth and lips daily for sores or other signs of stomatitis. ■ Prophylactic antiemetics may reduce nausea and vomiting and increase patient comfort. ■ Toxicity increased by any form of therapy that adds to stress, poor nutrition, and bone marrow suppression. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood). ■ See Drug/Lab Interactions.
Effective birth control recommended. ■ See Appendix D, p. 1311. ■ Report IV site burning and stinging promptly. ■ Drink at least 2 liters of fluid each day.
Category D: avoid pregnancy; can cause fetal harm. ■ Discontinue breast-feeding. ■ Safety for use in pediatric patients not established.
May be more sensitive to toxic effects of the drug. Consider age-related organ impairment. ■ See Dose Adjustments.
Potentiates anticoagulants.■ Do not administer live virus vaccines to patients receiving antineoplastic drugs. ■ Cimetidine (Tagamet), interferon-alfa, and leucovorin calcium may increase toxicity. ■ Additive bone marrow suppression may occur with radiation therapy, other bone marrow–suppressing agents (e.g., azathioprine, chloramphenicol, irinotecan, melphalan, vinorelbine), and/or agents that cause blood dyscrasias (e.g., metronidazole). ■ Thiazide diuretics (e.g., chlorothiazide) may prolong antineoplastic-induced leukopenia. ■ May decrease metabolism and increase serum levels of phenytoin.
Abnormal bromsulphalein (BSP), prothrombin, total protein, sedimentation rate; alopecia (reversible), anaphylaxis, bleeding, bone marrow suppression (agranulocytosis, anemia, leukopenia, pancytopenia, thrombocytopenia), cerebellar syndrome, cramps, dermatitis, diarrhea, disorientation, dry lips, erythema, esophagopharyngitis and stomatitis (may lead to sloughing and ulceration), euphoria, frequent stools, GI ulceration and bleeding, headache, hemorrhage from any site, increased skin pigmentation, infection, lacrimal duct stenosis, mouth soreness and ulceration, myocardial ischemia, nail changes, nausea, palmar-plantar erythrodysesthesia syndrome (tingling of hands and feet followed by pain, redness, and swelling), photophobia, photosensitivity, pneumopathy (cough, shortness of breath), thrombophlebitis, visual changes, vomiting (intractable). Diarrhea and stomatitis are most common and may be more severe with a prolonged duration in patients on combination therapy. Pseudomembranous colitis has been reported.
Keep physician informed of any side effects. Discontinue the drug and notify physician promptly at the first sign of toxicity (e.g., bleeding, diarrhea, esophagopharyngitis, gastritis, intractable vomiting, rapidly falling white count, sores in or around the lips or mouth, stomatitis). Nadir of leukocyte count occurs around Days 9 to 14. Recovery should be by Day 30. Discontinue the drug if the WBC count is less than 3,500/mm3 or platelets are less than 100,000/mm3; should reach 4,000/mm3 and 130,000/mm3 respectively in 2 weeks; if they do not, discontinue treatment. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes, and/or blood modifiers [e.g., darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim, sargramostim]) may be indicated to treat bone marrow toxicity. Continue to monitor for 4 weeks. Palmar-plantar erythrodysesthesia syndrome has been treated with oral pyridoxine (vitamin B6), 100 to 150 mg daily. Death may occur from the progression of many side effects. There is no specific antidote; supportive therapy as indicated will help sustain the patient in toxicity.