Floxuridine

Class: Antineoplastic Agents
VA Class: AN300
Chemical Name: 2′-Deoxy-5-fluorouridine
Molecular Formula: C9H11FN2O5
CAS Number: 50-91-9

Warning(s)

  • Only for administration by, or under the supervision of, a clinician experienced in cancer chemotherapy (including the use of antimetabolites) and in intra-arterial drug therapy.105

  • Severe toxic reactions are possible; hospitalize patient during initial course of treatment.105

Introduction

Pyrimidine antagonist; antimetabolite; antineoplastic agent.105

Uses for Floxuridine

GI Adenocarcinoma

Palliative management of GI adenocarcinoma that has metastasized to the liver and is considered incurable by surgery or other means of cancer therapy.102 105

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Not intended for use as adjuvant to surgery.105

In patients with carcinoma extending beyond area capable of being infused via a single artery, consider using other systemic chemotherapeutic agents.105

Liver Cancer

Palliative management of liver cancer; usually administered by hepatic intra-arterial infusion.102

Floxuridine Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.105

Administration

Intra-arterial Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by continuous regional intra-arterial infusion via a catheter inserted into the arterial blood supply of the tumor.105 a

Use an appropriate infusion pump to overcome pressure in large arteries and to ensure uniform rate of infusion.105

Sterile water for injection may be infused between courses to keep catheter open.a

Reconstitution

Reconstitute vial containing 500 mg of floxuridine with 5 mL of sterile water for injection to provide a solution containing 100 mg/mL.105

Dilution

Dilute calculated daily dose with 5% dextrose or 0.9% sodium chloride injection to a volume appropriate for infusion apparatus used.105

Dosage

Adults

GI Adenocarcinoma
Intra-arterial

0.1–0.6 mg/kg daily.105

For hepatic artery infusion, use higher dosages (0.4–0.6 mg/kg daily); the liver metabolizes the drug, thus reducing risk of systemic toxicity.105

Continue therapy until toxicity occurs (see General Precautions under Cautions);105 1–6 weeks of continuous administration generally adequate.a Maintain therapy as long as response continues.105

Cautions for Floxuridine

Contraindications

  • Poor nutritional state.105

  • Depressed bone marrow function (leukocyte count ≤5000/mm3 and/or a platelet count ≤100,000/mm3).a

  • Potentially serious infections.a

Warnings/Precautions

Warnings

Prior Use of Irradiation Therapy or Alkylating Agents

Use with extreme caution in patients who have previously received high-dose pelvic irradiation therapy or alkylating agents.105

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.105

Avoid pregnancy during therapy.105 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.105

Toxicity Potentiation with Concomitant Therapy

Increased risk of toxicity if used with any form of therapy that adds to the stress of the patient, interferes with nutrition, or depresses bone marrow function.105

Sensitivity Reactions

Localized erythema, alopecia, dermatitis, rash, edema, excoriation, maceration, pruritus, ulceration, and nonspecific skin reactions reported.105 106

Anaphylaxis, generalized allergic reactions, and photosensitivity reported with fluorouracil; potential for similar sensitivity reactions with floxuridine due to pharmacologic similarity with fluorouracil.105

General Precautions

Toxicity

Toxic effects following intra-arterial infusion generally related to the drug-infused area;105 however, systemic toxicity has been reported.105

Floxuridine is metabolized to fluorouracil, but the full spectrum of fluorouracil toxicity is not expected due to regional administration of the drug.105 Consider the possibility of typical adverse effects of fluorouracil during floxuridine therapy.105

May produce severe hematologic toxicity, GI hemorrhage, and even death.105

Adequate Patient Evaluation and Monitoring

Therapeutic response is not likely to occur without some evidence of toxicity (e.g., adverse hematologic or GI effects).105 (See Toxicity under Cautions.)

Severe toxicity more likely to occur in poor-risk patients (e.g., poor nutritional state, depressed bone marrow function, concurrent serious infections) (see Contraindications); however, possible death (despite careful patient selection and dosage adjustment) even in patients in relatively good condition.105

Monitor patients carefully due to narrow margin of safety.105

Hematologic Effects

Anemia, leukopenia, and thrombocytopenia reported.105 Carefully monitor WBC and platelet counts.105

Discontinue promptly for leukopenia (WBC <3500/mm3) or if WBC decreases rapidly.105

Discontinue promptly for thrombocytopenia (platelets <100,000/mm3).105

Discontinue promptly for hemorrhage at any site.105

May resume therapy when manifestations have resolved.105

GI Effects

Nausea, vomiting, diarrhea, enteritis, stomatitis, duodenal ulcer, duodenitis, gastritis, GI bleeding, gastroenteritis, glossitis, pharyngitis, anorexia, cramps, and abdominal pain reported.105

Discontinue promptly for stomatitis or esophagopharyngitis.a

Discontinue promptly for intractable vomiting.105

Discontinue promptly for GI ulceration and bleeding.105

May resume therapy when manifestations have resolved.105

Cardiovascular Effects

Discontinue promptly if myocardial ischemia occurs.105 May resume therapy when manifestations have resolved.105

Hepatic Effects

Acalculus cholecystitis and elevations in serum alkaline phosphatase, aminotransferase, bilirubin, and LDH concentrations reported.105

With hepatic arterial infusion, possible intra- and/or extrahepatic biliary sclerosis100 101 103 104 105 and liver cirrhosis.101 103

Local and Regional Effects

Arterial aneurysm, arterial ischemia, arterial thrombosis, bleeding at catheter site, blocked/displaced/leaking catheter, embolism, fibromyositis, infection at catheter site, hepatic necrosis, abscesses, and thrombophlebitis reported.105 Inaccurate catheter placement and contamination of infusion assembly also reported.10

Specific Populations

Pregnancy

Category D.105 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether floxuridine is distributed into milk.105 Discontinue nursing.105

Pediatric Use

Safety and efficacy not established.105

Hepatic Impairment

Use with extreme caution.105

Renal Impairment

Use with extreme caution.105

Common Adverse Effects

Nausea, vomiting, diarrhea, enteritis, stomatitis, localized erythema, anemia, leukopenia, thrombocytopenia, elevated hepatic enzyme concentrations.105

Interactions for Floxuridine

Increased risk of toxicity if used with any form of therapy that adds to the stress of the patient, interferes with nutrition, or depresses bone marrow function.105

Floxuridine Pharmacokinetics

Elimination

Metabolism

Following continuous intra-arterial infusion, floxuridine is anabolized to active metabolite floxuridine-monophosphate (FUDR-MP).105 Following rapid intra-arterial injection, the drug is catabolized to fluorouracil.105

Metabolized in the liver.105 Less metabolic degradation following intra-arterial continuous infusion than following rapid injection.a

Elimination Route

Excreted intact in urine as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine; also excreted as respiratory carbon dioxide.105

Stability

Storage

Parenteral

Powder for Injection

15–30°C.105

Reconstituted solution: 2–8°C for ≤2 weeks.105

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility105

Compatible

Dextrose 5%

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Carboplatin

Cisplatin

Cisplatin with etoposide

Cisplatin with leucovorin calcium

Etoposide

Fluorouracil

Leucovorin calcium

Y-Site CompatibilityHID

Compatible

Amifostine

Aztreonam

Etoposide phosphate

Filgrastim

Fludarabine phosphate

Gemcitabine HCl

Granisetron HCl

Melphalan HCl

Ondansetron HCl

Paclitaxel

Piperacillin sodium–tazobactam sodium

Sargramostim

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Cefepime HCl

Actions

  • Inhibits DNA synthesis and, to a lesser extent, RNA formation.105

  • Active metabolite FUDR-MP inhibits thymidylate synthetase (thus inhibiting methylation of deoxyuridylic acid to thymidylic acid),a resulting in inhibition of DNA synthesis.105

  • Produces the same antimetabolic effects as fluorouracil105 (i.e., blocks uracil riboside phosphorylase, thus inhibiting utilization of preformed uracil in RNA synthesis).a Metabolites of fluorouracil become incorporated to a small extent into RNA, producing fraudulent RNA.a

Advice to Patients

  • Risk of severe adverse hematologic (e.g., anemia, leukopenia, thrombocytopenia) and GI effects (e.g., vomiting, diarrhea, stomatitis, esophagopharyngitis).105

  • Risk of transient alopecia.105

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.105

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.105 Necessity for clinicians to advise women to avoid pregnancy during therapy; advise pregnant women of risk to the fetus.105

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Floxuridine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for intra-arterial infusion only

500 mg*

Floxuridine for Injection

Abraxis, Bedford

FUDR

Mayne

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

3. Papac RJ, Calabresi P. Infusion of floxuridine in the treatment of solid tumors. JAMA. 1966; 197:237-41. [PubMed 4287261]

10. Sullivan RD, Watkins E Jr, Oberfield RA et al. Current status of protracted arterial infusion cancer chemotherapy for the treatment of solid tumors. Surg Clin North Am. 1967; 47:769-83. [PubMed 6022984]

12. Cangir A, Sullivan MP, Sutow WW et al. Cytomegalovirus syndrome in children with acute leukemia. JAMA. 1967; 201:612-5. [PubMed 4378187]

13. Ansfield FJ, Curreri AR. Further clinical comparison between 5-fluorouracil (5-FU) and 5-fluoro-2′-deoxyuridine. Cancer Chemother Rep. 1963; 32:101-5. [PubMed 14088828]

14. Curreri AR, Ansfield FJ. Comparison of 5-fluorouracil (5-FU) and 5-fluoro-2′-deoxyuridine in the treatment of far-advanced breast and colon lesions. Cancer Chemother Rep. 1962: 16:387-8.

20. Ansfield FJ, Curreri AR. Clinical studies with 5-fluoro-2′-deoxyuridine. Cancer Chemother Rep. 1960; 6:21-5. [PubMed 13793784]

29. Dao TL, Grinberg R. Fluorinated pyrimidines in treatment of breast cancer patients with liver metastases. Cancer Chemother Rep. 1963; 27:71-7. [PubMed 14025064]

32. Young CW et al. The clinical evaluation of 5-fluorouracil and 5-fluoro-2′-deoxyuridine in solid tumors and adults. Cancer Chemother Rep. 1960; 6:17-20. [PubMed 13846613]

33. Nevinny HB. Comparative study of 5-fluorouracil (FU), 5-fluorodeoxyuridine (FUDR), and methotrexate (MTX) in patients with advanced cancer. Proc Annu Meet Am Assoc Cancer Res. 1964; 5:47.

34. Hartman JR et al. The clinical evaluation of 5-fluoro-2′-deoxyuridine in acute leukemia in children. Cancer Chemother Rep. 1960; 8:84-96. [PubMed 14400172]

35. Couture J. Intra-arterial infusion therapy for oral cancer. Can J Surg. 1968; 11:420-3. [PubMed 5683599]

36. Sullivan RD. Protracted arterial infusion chemotherapy in head and neck cancer. Med Sci. 1967; 18:35-40.

100. Hohn D, Melnick J, Stagg R et al. Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine. J Clin Oncol. 1985; 3:98-102. [PubMed 3155548]

101. Pettavel J, Gardiol D, Bergier N et al. Fatal liver cirrhosis associated with long-term arterial infusion of floxuridine. Lancet. 1986; 2:1162-3. [IDIS 223326] [PubMed 2877311]

102. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

103. Doria MI, Shepard KV, Levin B et al. Liver pathology following hepatic arterial infusion chemotherapy: hepatic toxicity with FUDR. Cancer. 1986; 58:855-61. [IDIS 219492] [PubMed 2941140]

104. Kemeny N, Daly J, Reichman B et al. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma: a randomized trial. Ann Intern Med. 1987; 107:459-65. [IDIS 234485] [PubMed 2957943]

105. Bedford Laboratories. Floxuridine for injection USP prescribing information. Bedford, OH; 2000 Feb.

106. Roche Laboratories. FUDR (floxuridine) prescribing information. Nutley, NJ; 1971 Feb.

a. AHFS drug information 2004. McEvoy GK, ed. Floxuridine. Bethesda, MD: American Society of Health-System Pharmacists; 2004:993-4.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:719-21.

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