5-fluorouracil [5-FU] (Fluoroplex, Efudex, Adrucel, Carac)

Introduction

Topical: Tradenames: Fluoroplex, Efudex.

Indications

• topical
  • multiple actinic keratosis
    • 1-2% 5-FU BID to lesions on head & neck
    • 5% 5-FU BID to other areas
  • superficial basal cell carcinoma
    • 5% 5-FU BID for 3-6 weeks
    • treatment for 10-12 weeks may be necessary
  • prevention of squamous cell carcinoma skin in high-risk patients
  • condyloma accuminata
  • verruca plana
  • leukoplakia
  • actinic cheilitis
  • radiodermatitis
• systemic chemotherapy for malignancy (Adrucel)
  • gastrointestinal carcinoma
    • colorectal carcinoma
    • esophageal carcinoma
    • gastric carcinoma
  • breast cancer
  • pancreatic cancer
    • islet cell tumor
  • head & neck cancer
  • liver cancer
  • biliary carcinoma
  • carcinoid syndrome
  • bladder cancer
  • cervical cancer
  • penile cancer

Dosage

Administration:

• topical
  • Wash hands after use.
  • Do not use occlusive dressings
  • 5% BID for 2-4 weeks (prevention of SCCS)

Cream: 1% (Fluoroplex), 5% (Efudex)

Solution: 1% (Fluroplex), 2% (Efudex), 5% (Efudex), 10 mL.

Pharmacokinetics

• widely distributed
• penetrates into CSF
• metabolized in liver
• eliminated in urine
• 1/2life is 10-15 minutes

Typical response (topical)

• erythema followed by scaling, tenderness, vesiculation, erosion, ulceration, necrosis, re-epithelialization
• therapy is continued until the erosion, ulceration, necrosis phase is reached
• normal skin should show little response to 5-FU
• initial combination therapy with tretinoin may be indicated
• complete healing may take 1-2 months & may be hastened by application of topical glucocorticoid after 5-FU has bee discontinued

elimination via liver

1/2life = 10-15 minutes

Adverse effects

• topical:
• no systemic toxicity reported
• one manufacturer lists leukopenia & thrombocytopenia
• local pain
• pruritus
• irritation
• photosensitivity
• systemic
  • common (> 10%)
    • diarrhea
    • heartburn
    • mucositis, stomatitis
    • nausea/vomiting
    • dermatitis
    • anorexia
    • alopecia
    • bone marrow suppression
    • vasospasm
  • not common (1-10%)
    • GI ulceration, dry skin
  • uncommon (< 1%)
    • shortness of breath, ataxia, paresthesias, cardiac arrhythmias, heart failure, hypotension, headache, hyperpigmentation of the skin, pruritic maculopapular rash, partial loss of fingernails &/or toenails, hyperpigmentation of fingernail &/or toenail bed, myelosuppression, hepatotoxicity, visual disturbances, photosensitivity
  • other
    • severe reaction in patients with DPYD deficiency
      • stomatitis, leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, neurologic symptoms, progressing to semicoma
    • heart failure (rare) from myocardial infarction during treatment
    • pseudo-porphyria cutanea tarda
    • cutaneous lupus erythematosus
    • hand-&-foot syndrome
    • excessive lacrimation
    • hyperpigmentation of palms (image)
• topical 5FU may be lethal if consumed by dog

Drug interactions

• cimetidine
• leucovorin

Laboratory

• see ARUP consult

Mechanism of action

• antimetabolite; inhibits thymidylate synthase
• interferes with DNA synthesis
• S-phase specific

Mechanism of drug resistance:

• increased activity of target enzyme thymidylate synthase
• alteration in target enzyme thymidylate synthase

More general terms

• fluoropyrimidine
• antineoplastic agent (chemotherapeutic agent)

Additional terms

• thymidylate synthase; TS; TSase (TYMS, TS, OK/SW-cl29)

Component of

• 5-fluorouracil/irinotecan/leucovorin/oxaliplatin (FOLFIRINOX)
• cyclophosphamide/methotrexate/5-fluorouracil (CMF)
• cyclophosphamide/doxorubicin (Adriamycin)/5-fluorouracil (CAF)
• cyclophosphamide/epirubicin/fluorouracil (CEF, FEC-100)
• 5-fluorouracil/oxaliplatin/leucovorin (FOLFOX)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281053
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3385