From the Guidelines
Fluorouracil (5-FU) should be administered at a dose of 400 mg/m² as a bolus followed by 2400-3000 mg/m² as a 46-hour continuous infusion every two weeks, as part of the FOLFOX or FOLFIRI regimens, for the treatment of colorectal cancer, based on the most recent and highest quality evidence 1.
Key Considerations
- The dose and regimen of fluorouracil may vary depending on the type of cancer being treated, with specific regimens for colorectal, breast, and other cancers.
- Combination chemotherapy with 5-FU/LV/oxaliplatin (FOLFOX) or 5-FU/LV/irinotecan (FOLFIRI) provides higher response rates, longer progression-free survival, and better survival than 5-FU/LV alone 1.
- The optimal duration of chemotherapy for metastatic CRC remains controversial, with options including a fixed treatment period or treatment until progression or toxicity 1.
- Regular monitoring of blood counts and liver function is essential during treatment with fluorouracil, and dose adjustments may be necessary for patients with renal or hepatic impairment.
Common Side Effects
- Myelosuppression
- Mucositis
- Diarrhea
- Hand-foot syndrome
Administration
- Central venous access is recommended for continuous infusions of fluorouracil.
- Topical 5-FU (5% cream or solution) is used for superficial skin cancers, applied twice daily for 2-4 weeks.
Mechanism of Action
- Fluorouracil works as an antimetabolite by inhibiting thymidylate synthase and incorporating into RNA and DNA, disrupting cellular function and leading to cancer cell death. The most recent evidence from 2022 1 supports the use of fluorouracil in combination with other agents, such as oxaliplatin and irinotecan, for the treatment of various cancers, including colorectal and gastric cancer.
From the FDA Drug Label
- DOSAGE & ADMINISTRATION 2.1 General Dosage Information Fluorouracil is recommended for administration either as an intravenous bolus or as an intravenous infusion. 2.2 Recommended Dosage for Adenocarcinoma of the Colon and Rectum • The recommended dose of fluorouracil, administered in an infusional regimen in combination with leucovorin alone, or in combination with leucovorin and oxaliplatin or irinotecan, is 400 mg/m2 by intravenous bolus on Day 1, followed by 2400 mg/m2 to 3000 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks 2.3 Recommended Dosage for Adenocarcinoma of the Breast The recommended dose of fluorouracil, administered as a component of a cyclophosphamide based multidrug regimen, is 500 mg/m2 or 600 mg/m2 intravenously on Days 1 and 8 every 28 days for 6 cycles 2.4 Recommended Dosage for Gastric Adenocarcinoma • The recommended dose of fluorouracil, administered as a component of a platinum-containing multidrug chemotherapy regimen, is 200 mg/m2 to 1000 mg/m2 intravenously as a continuous infusion over 24 hours. 2.5 Recommended Dosage for Pancreatic Adenocarcinoma • The recommended dose of fluorouracil, administered as an infusional regimen in combination with leucovorin or as a component of a multidrug chemotherapy regimen that includes leucovorin, is 400 mg/m2 intravenous bolus on Day 1, followed by 2400 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.
The recommended use and dosage of fluorouracil in cancer treatment varies depending on the type of cancer.
- Adenocarcinoma of the Colon and Rectum: 400 mg/m2 by intravenous bolus on Day 1, followed by 2400 mg/m2 to 3000 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.
- Adenocarcinoma of the Breast: 500 mg/m2 or 600 mg/m2 intravenously on Days 1 and 8 every 28 days for 6 cycles.
- Gastric Adenocarcinoma: 200 mg/m2 to 1000 mg/m2 intravenously as a continuous infusion over 24 hours.
- Pancreatic Adenocarcinoma: 400 mg/m2 intravenous bolus on Day 1, followed by 2400 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks. 2
From the Research
Recommended Use of Fluorouracil
- Fluorouracil is widely used in the management of several common malignancies, including cancer of the colon, breast, and skin 3.
- It is commonly used in the treatment of colorectal cancer, either as a single agent or in combination with other chemotherapy agents 4, 5, 6.
Dosage of Fluorouracil
- The optimal therapeutic dosage of fluorouracil is equivalent to an AUC (area under the plasma concentration-time curve) of 28.03-38.94 mg·h/L 5.
- The dosage of fluorouracil can vary depending on the route of administration, with oral administration resulting in variable plasma levels and bioavailability 7.
- Parenteral administration, either intravenously or through hepatic arterial infusion, is commonly used to achieve higher plasma levels of the drug 3, 6.
Administration Routes
- Fluorouracil can be administered orally, intravenously, or through hepatic arterial infusion 3, 6, 7.
- Oral administration has variable bioavailability, while intravenous administration results in higher plasma levels 7.
- Hepatic arterial infusion is a viable option for patients with colorectal cancer, allowing for higher concentrations of the drug to be delivered directly to the tumor site 3, 6.
Toxicity and Efficacy
- The toxicity and efficacy of fluorouracil can vary greatly among individuals, suggesting a need for individualized treatment regimens 5.
- Monitoring of plasma levels of the drug in individual patients may be useful to optimize treatment efficacy and minimize toxicity 7.
- Alternative treatment options, such as capecitabine or raltitrexed, may be considered for patients who experience cardiotoxicity or other adverse effects with fluorouracil 4.