About This Guide

This guide provides supporting clinical context for the 5-Fluorouracil (5-FU) Dose Calculator. The information below details the calculator's functions, the clinical parameters it uses, and general principles of 5-FU administration and safety. It is intended for healthcare professionals as an educational supplement to, not a replacement for, clinical judgment and institutional protocols.

Outputs

After entering the required patient data and selecting a regimen, the calculator provides the following key outputs:

  • Body Surface Area (BSA): Calculated using the selected formula (e.g., Mosteller, Du Bois), displayed in m².
  • Creatinine Clearance (CrCl): Estimated using the Cockcroft-Gault equation unless a manual value is provided, displayed in mL/min.
  • 5-FU IV Bolus Dose: The total calculated dose in milligrams (mg) for the bolus component of the selected regimen, adjusted for BSA and any specified dose modifications.
  • 5-FU Infusion Dose: The total calculated dose in milligrams (mg) for the continuous infusion component, including the specified duration (e.g., "over 46 hours").
  • Dose Adjustments Summary: A summary of any dose reductions applied, such as those for DPD deficiency, hepatic impairment, or prior toxicity.
  • Infusion Rate: If infusion volume and drug concentration are provided, the calculator computes the final infusion rate in mL/hr.

How to Use

To ensure accurate dose calculation, follow these steps:

  1. Enter Patient Data: Input the patient's height, weight, age, sex, and serum creatinine. Ensure the correct units (e.g., cm/in, kg/lbs, mg/dL/μmol/L) are selected. Choose the preferred BSA calculation formula.
  2. Select Regimen: Choose between "Common Regimens" or "Custom Dose". For common regimens, select from the provided list (e.g., FOLFOX, FOLFIRI). For a custom dose, enter the dose in mg/m² and specify the administration type (bolus or infusion with duration).
  3. Apply Dose Modifications (Optional): In the adjustments section, indicate any known DPD deficiency, elevated total bilirubin levels, or toxicity from a prior cycle. These selections will trigger evidence-based dose reductions.
  4. Calculate Infusion Rate (Optional): If you need to determine the pump rate, enter the total final volume of the infusion bag (in mL) and the concentration of 5-FU (in mg/mL).
  5. Calculate and Review: Click the calculate button to see the results. Always verify the calculated doses against the patient's clinical status, institutional guidelines, and the primary literature before ordering or administering the medication.

Dosing Overview

5-Fluorouracil is an antimetabolite cytotoxic agent whose dosing is highly dependent on the treatment protocol, patient-specific factors, and toxicity profile. Doses are almost always calculated based on the patient's BSA.

  • Regimens: The calculator includes several standard chemotherapy regimens, such as FOLFOX and FOLFIRI, which combine 5-FU with other agents like oxaliplatin and irinotecan. These protocols have specific doses for both the initial IV bolus and the subsequent continuous infusion.
  • BSA Calculation: BSA is a critical factor for accurate dosing. The Mosteller formula is widely used for its simplicity, but the calculator offers other options like Du Bois for institutional preference.
  • Renal and Hepatic Function: While 5-FU is primarily cleared by the liver, severe renal impairment can influence tolerance. The tool calculates CrCl for a complete patient assessment. Significant hepatic impairment (elevated bilirubin) requires mandatory dose reduction or discontinuation, which the tool accounts for.

Switching or Modifying Doses

Dose modifications between treatment cycles are common and necessary to manage toxicities. The calculator assists with this by allowing users to specify the type and grade of toxicity experienced in a prior cycle (e.g., Grade 2 stomatitis, Grade 3 diarrhea). Based on CTCAE standards, the tool will apply a percentage-based reduction to the next cycle's dose. Switching between entire regimens (e.g., from FOLFOX to FOLFIRI) is a clinical decision based on disease progression or unacceptable toxicity and should be done under the guidance of an oncologist.

Missed Dose

Management of a missed or delayed 5-FU dose depends on the clinical context, including whether it is the bolus or part of the continuous infusion. There is no single rule for this scenario. The patient's oncologist and clinical team must be consulted immediately to determine the appropriate course of action, which may involve dose omission, rescheduling, or other adjustments based on the specific treatment plan and timing.

Safety Alerts

Dihydropyrimidine Dehydrogenase (DPD) Deficiency

DPD deficiency is a critical safety issue. DPD is the primary enzyme responsible for metabolizing 5-FU. Patients with partial or complete DPD deficiency are at high risk of severe, life-threatening, or fatal toxicity (e.g., severe mucositis, diarrhea, neutropenia) if given standard doses. The tool includes a checkbox to apply a significant dose reduction (typically at least 50%) for patients with known or suspected deficiency. Pre-treatment testing for DPD deficiency is recommended by many regulatory bodies.

Hepatic Impairment

As 5-FU is metabolized in the liver, significant hepatic dysfunction can lead to increased drug exposure and toxicity. The calculator incorporates dose reductions based on total bilirubin levels, consistent with standard clinical guidelines. Doses may be reduced by 25-50% or held entirely for severe impairment.

Frequently Asked Questions

  • Which BSA formula should I use?

    The Mosteller formula is the most common default due to its simplicity and validation. However, your institution may have a standard protocol that requires a different formula like Du Bois. Consistency is key.

  • How does the calculator account for renal function?

    The tool calculates CrCl via Cockcroft-Gault to provide a full clinical picture. While 5-FU itself doesn't typically require dose adjustment for renal impairment, co-administered drugs in regimens like FOLFOX (e.g., oxaliplatin) might. This value helps in overall patient assessment.

  • Why is there a DPD deficiency checkbox?

    This is a critical safety feature. Checking this box applies a significant dose reduction (e.g., 50%) to mitigate the risk of severe toxicity in patients who cannot properly metabolize 5-FU. This should only be used based on genetic testing or strong clinical suspicion.

  • What happens if I enter a high bilirubin value?

    The calculator will automatically reduce the calculated dose based on the severity of hyperbilirubinemia. For bilirubin levels >5.0 mg/dL, it will likely recommend holding the dose, as this indicates severe hepatic dysfunction.

  • Can this calculator be used for capecitabine?

    No. Capecitabine is an oral prodrug of 5-FU with its own distinct dosing guidelines based on BSA and renal function (CrCl). This calculator is only for intravenous 5-Fluorouracil.

  • What is the difference between the FOLFOX and FOLFIRI regimens?

    Both use the same 5-FU dosing (400 mg/m² bolus followed by a 2400 mg/m² infusion over 46 hours). The difference is the accompanying chemotherapy agent: FOLFOX includes Oxaliplatin, while FOLFIRI includes Irinotecan.

  • Does the "Mayo Clinic" regimen not have an infusion?

    Correct. The Mayo Clinic regimen is a historical protocol that uses a daily bolus of 5-FU (with leucovorin) for five consecutive days, without a continuous infusion component.

  • The infusion rate calculation shows a warning. What does it mean?

    A warning appears if the volume of drug needed to supply the total dose (based on the entered concentration) is greater than the total infusion volume you specified. This indicates a potential error in the volume or concentration values entered.

References

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