Floxuridine (FUDR) is an antimetabolite drug that is administered intra-arterial for hepatic metastasis of colorectal carcinoma.

Floxuridine (FUDR) Indications:

• Colorectal cancer with hepatic metastases:

  • Used for the palliative management of hepatic metastases of colorectal cancer (administered by continuous regional hepatic intra-arterial infusion) in select patients considered incurable by surgical resection or other means.
  • Limitation of use:
    • Patients with known disease extending beyond an area capable of a single artery infusion should (in most cases) be considered for systemic chemotherapy with other agents.

Floxuridine (FUDR) Dose in Adults

Floxuridine (FUDR) Dose in the treatment of colorectal cancer with hepatic metastases:

• Hepatic intra-arterial (off-label combination):
  • 0.25 mg/kg/day (with dexamethasone and heparin) continuous infusion for 14 days during a 5-week cycle for 6 cycles (in combination with 6 cycles of fluorouracil and leucovorin; begin floxuridine 2 weeks after the fluorouracil and leucovorin cycle).

• Manufacturer’s labeling:

  • Dosing in the prescribing information may not reflect current clinical practice.
  • Range: 0.1 to 0.6 mg/kg/day as a continuous infusion;
  • Usual dose: 0.4 to 0.6 mg/kg/day as a continuous infusion;
  • continue until intolerable toxicity.

Use in Children:

Not indicated.

Pregnancy Risk Factor D

• Humans are known to be teratogenic for drugs that inhibit DNA synthesis.
• Females with reproductive potential should not get pregnant while receiving floxuridine treatment.
• Animal reproduction studies have shown adverse effects.
• If Floxuridine is administered during pregnancy, it can cause harm to the fetus.

Use of loxuridine while breastfeeding

• The manufacturer suggests against breastfeeding while receiving floxuridine treatment.

Dose in Kidney Disease:

Manufacturer’s labeling doesn't provide and dosage adjustments; Use with extreme caution

Floxuridine (FUDR) Dose in Liver disease:

• Manufacturer’s labeling doesn't provide and dosage adjustments;
• Use with extreme caution.
• Dosage adjustments for hepatic impairment have been described in literature.

• Floyd 2006:

  • Serum bilirubin 1.2 x ULN or alkaline phosphatase 1.2 x ULN:
    • Administer 80% of the dose.
  • Serum bilirubin 1.5 x ULN; transaminases 3 x baseline or alkaline phosphatase 1.5 x ULN:
    • Administer 50% of the dose.
  • Serum bilirubin 2 x ULN; transaminases >3 x baseline or alkaline phosphatase 2 x ULN:
    • No recommendation is available.
• Zalcberg 2004 (baseline is the value obtained on the day of the last floxuridine dose; dosage adjustment based on value on the pump emptying day or planned treatment day [whichever is higher]):

  • AST:

    • If baseline AST was ≤50 units/L:
      • Administer 80% of the dose if AST is 3 to <4 x the baseline value, and administer 50% of the dose if AST is 4 to <5 x the baseline value.
      • If AST is ≥5 x the baseline value, hold floxuridine.
      • May restart floxuridine at 50% of the last dose administered when AST is <4 x the baseline value.
    • If baseline AST was >50 units/L:
      • Administer 80% of the dose if AST is 2 to <3 x the baseline value, and administer 50% of the dose if AST is 3 to <4 x the baseline value.
      • If AST is ≥4 x the baseline value, hold floxuridine.
      • May restart floxuridine at 50% of the last dose administered when AST is <3 x the baseline value.

  • Alkaline phosphatase:

    • If baseline alkaline phosphatase was ≤90 units/L:
      • Administer 50% of the dose if alkaline phosphatase is 1.5 to <2 x the baseline value.
      • If alkaline phosphatase is ≥2 x the baseline value, hold floxuridine.
      • May restart floxuridine at 25% of the last dose administered when alkaline phosphatase is <1.5 x the baseline value.
    • If baseline alkaline phosphatase was >90 units/L:
      • Administer 50% of the dose if alkaline phosphatase is 1.2 to <1.5 x the baseline value.
      • If alkaline phosphatase is ≥1.5 x the baseline value, hold floxuridine.
      • May restart floxuridine at 25% of the last dose administered when alkaline phosphatase is <1.2 x the baseline value.

  • Total bilirubin:

    • If the baseline total bilirubin was ≤1.2 mg/dL:
      • Administer 50% of the dose if bilirubin is 1.5 to <2 x the baseline value.
        • If bilirubin is ≥2 x the baseline value, hold floxuridine.
        • May restart floxuridine at 25% of the last dose administered when total bilirubin is <1.5 x the baseline value.
    • If baseline total bilirubin was >1.2 mg/dL:
      • Administer 50% of the dose if bilirubin is 1.2 to <1.5 x the baseline value.
      • If bilirubin is ≥1.5 x the baseline value, hold floxuridine.
      • May restart floxuridine at 25% of the last dose administered when total bilirubin is <1.2 x the baseline value.

Common Side Effects of Floxuridine (FUDR):

• Gastrointestinal:

  • Diarrhea (May Be Dose Limiting)
  • Stomatitis

• Hematologic & Oncologic:

  • Anemia
  • Bone Marrow Depression (Nadir: 7-10 Days; May Be Dose Limiting)
  • Leukopenia
  • Thrombocytopenia

Less Common Side Effects Of Floxuridine (FUDR):

• Dermatologic:

  • Alopecia
  • Dermatitis
  • Localized Erythema
  • Skin Hyperpigmentation
  • Skin Photosensitivity

• Gastrointestinal:

  • Anorexia
  • Biliary Sclerosis
  • Cholecystitis

• Hepatic:

  • Jaundice

Contraindications to Floxuridine (FUDR):

• Inadequate nutrition;
• Potentially deadly infections
• Function of the bone marrow is depressed

Warnings and precautions

• Suppression of bone marrow

  • Floxuridine can cause severe leukopenia and hematologic toxicities.
  • Anemia and thrombocytopenia are common.
  • The nadir is typically between 7 and 10 days. Therapy discontinuation may be necessary for thrombocytopenia or leukopenia.

• Cardiovascular toxicities:

  • There have been reports of myocardial ischemia. If this happens, discontinue or avoid immediately.

• Gastrointestinal toxicities:

  • Could cause gastrointestinal toxicities.
  • Stop if you feel that you are experiencing stomatitis, esophagopharyngitis or other symptoms.
  • For severe vomiting, diarrhea, and gastrointestinal ulceration/bleeding, discontinue use.

• Hemorrhage

  • If hemorhage occurs (from any site), discontinue use
  • There may be bleeding.

• Toxicity

  • It is possible for toxicities to occur. Keep an eye out.
  • Patients at high risk are more likely to experience severe toxicities, as well as patients who have had prior alkylating agent use, and patients who have had previous pelvic radiation.

• Hepatic impairment

  • Patients with severe hepatic impairment should use it with caution.

• Renal impairment

  • Patients with severe renal impairment should be cautious.

Floxuridine: Drug Interaction

Monitoring parameters:

• Monitor CBC with differential and platelet count;
• liver function (phosphatase, bilirubin, alkaline and transaminases);
• monitor for signs and symptoms of gastrointestinal ulceration or bleeding, stomatitis or esophagopharyngitis, hemorrhage, vomiting, and/or diarrhea.

How to administer Floxuridine (FUDR)?

Administer as a continuous hepatic intra-arterial infusion using an infusion pump.

Mechanism of action of Floxuridine (FUDR):

• After intra-arterial administration of fluorouracil, Floxuridine is catabolized into fluorouracil.
• This results in an activity similar to fluorouracil. It also inhibits thymidylate synthesis and disrupts DNA/RNA synthesis.

Metabolism:

• It is metabolized by the liver to active metabolites (Floxuridine monophosphate, FUDR-MP and fluorouracil), and inactive metabolites ("Urea, CO2, afluorob-alanine and afluorob-guanidopropionic and ureidopropionic acids, respectively)

Excretion:

• Urine (as fluorouracil and urea), afluorob-alanine; afluorob-guanidopropionic Acid, afluorob-ureidopropionic Acid, and dihydrofluorouracil. Respiratory (as exhaled gases [CO2]).

International Brand Names of Floxuridine:

• FUDR

Floxuridine Brand Names in Pakistan:

There is no brand of Floxuridine available in Pakistan.