Topical Fluorouracil

Patient counseling on topical fluorouracil (5-FU) for cancerous lesions:


FDA approved for: actinic keratosis, superficial basal cell carcinoma

Mechanism of Action:
anti-metabolite & anti-neoplastic agent
Topically, as fluorouracil is metabolized it blocks a methylation reaction of deoxyuridylic acid to thymidylic acid, leading to an interference in the synthesis of DNA and RNA due to a deficiency in thymine. Ultimately this leads to cell death. This mechanism occurs more potently on rapidly dividing cells (cancerous cells) due to more rapid uptake of drug.
Dosing/administration:

• actinic keratosis: apply to lesions with either 0.5-5% cream BID for 2-6 weeks
• 0.5% microsphere formulation once daily for 4 weeks
• superficial basal cell carcinoma: apply to lesions with 5% cream BID for 3-12 weeks

*can be used off-label for other cancers

Common adverse effects: alopecia, photosensitvity, hand-foot syndrome, maculopapular inflammation, temporary reversible onycholysis and onychodystrophy, telangiectasia, scarring

Pregnancy category: X

Even though topical - can still cause drug interactions:
phenytoin/fosphyentoin - 5FU may increase phenytoin levels
gemcitabine - may increase 5FU levels
leucovorin - may increase toxicity associated with 5FU
vitamin K antagonists - 5Fu may increase serum concentrations of warfarin

ADME: Cmax ~ 1 hour after application of cream

Cost:

• Cream: $180.00-2997.18, varies based on brand and strength of product
• Solution: $75-111.33 

Counseling Pearls:

• Use non-metal applicator or gloves to apply. If used hands, wash hands immediately after application
• Try to shower/bath before application. If apply before, let areas dry, wait awhile before showering/bathing
• May cause sun sensitivity -- make sure to cover up, use sunscreen, avoid tanning beds
• Avoid application to mucous membranes (eyes, nose, mouth) or irritated skin
• May cause inflammation or allergic contact dermatitis
• chemotherapeutic drug -- cannot be disposed of in regular trash (ex: take back to pharmacy for disposal)
• Should be handled by pregnant or women of child-bearing age
• can cause birth defects
• do not use with occlusive dressings

Basal cell carcinoma background information:

• skin cancer that arises from the basal cell layer of the epidermis
• choice of treatment depends on size, location, and pathology of lesions
• Alternative therapies: surgical excision, Mohs surgery, electrodesiccation and curettage, cryosurgery, imiquimod. photodynamic therapy, radiation therapy, intralesional interferon, intralesional 5-FU, intralesional bleomycin
• treatment with 5FU --
• should be restricted to superficial lesions in non-critical areas
• low cure rates with non-superficial or high-risk lesions
• contraindicated for nodular lesions
• has long-term favorable cosmetic results compared to other therapy options
• although scarring may occur
• second-line therapy after electrodesiccation and curettage (first-line therapy) for superficial lesions
• Prognosis is usually excellent due to lesions being relatively slow growing tumors
• metastasis is rare, mortality is low, but morbidity is high
• if metastasis occurs --> poor prognosis
• can cause severe disfigurement, can destroy bone and cartilage, may cause ulcers leading to wound care
• 15% of patients will develop a new subsequent skin cancer within 1 year

References:

Product Information: fluorouracil IV injection solution, fluorouracil IV injection solution. Sandoz Inc (per DailyMed), Princeton, NJ, 2011.

Chartier T. Treatment and prognosis of basal cell carcinoma at low risk of recurrence. UpToDate. Stern R (Ed). Accessed on: 11/9/16