How do I use Effudex (5% fluorouracil) cream to treat a histologically confirmed superficial basal cell carcinoma in an adult who is not pregnant, not breastfeeding, and not severely immunocompromised?

How to Use Effudex (5-Fluorouracil 5% Cream) for Superficial Basal Cell Carcinoma

Apply Effudex 5% cream twice daily to the lesion and surrounding area for up to 12 weeks, continuing until clinical resolution occurs, then surgically excise the site 3 weeks post-treatment for histologic confirmation of cure. 1, 2

Patient Selection and Contraindications

Reserve Effudex for superficial basal cell carcinoma only when surgery or radiation is contraindicated or impractical, as cure rates are lower than surgical options (approximately 90-93% versus nearly 100% with surgery). 3, 1, 2

Absolute Contraindications:

• High-risk features: lesions ≥2 cm diameter, poorly defined borders, recurrent tumors, perineural invasion 4
• Nodular or infiltrative basal cell carcinoma subtypes 4, 1
• Severely immunocompromised patients 4
• Facial or neck nodular carcinomas (except under unusual circumstances with mandatory histologic follow-up) 5

Ideal Candidates:

• Small superficial basal cell carcinoma on trunk or limbs 2
• Multiple lesions where surgery is impractical 1
• Patients who refuse or cannot tolerate surgery 4

Application Protocol

Apply twice daily directly to the lesion and a small margin of surrounding skin for up to 12 weeks. 1, 2, 6

• Mean time to clinical cure is 10.5 weeks 2
• Treatment may be stopped sooner if the lesion clinically resolves 2
• An alternative regimen of once daily application for 6 weeks has been used in comparative trials, though twice daily for 4-12 weeks is more standard 6, 2

Expected Local Reactions

Moderate to severe local reactions including erythema, erosion, crust formation, swelling, and itching are expected and do not require discontinuation. 6

• Local skin redness is the most common reaction 6
• Erosion and crust formation occur more frequently with fluorouracil than with photodynamic therapy 6
• Most patients experience only mild erythema with no pain or scarring 2
• Local wound infection requiring outpatient treatment occurs rarely (approximately 1% of cases) 6

Critical Management Steps

Mandatory Histologic Confirmation:

Surgically excise the treated site 3 weeks after completing treatment for histologic evaluation—clinical appearance alone is insufficient to confirm cure. 2, 4

• Histologic cure rate is 90% (28/31 lesions) in the highest quality study 2
• Clinical clearance does not guarantee histologic clearance 4

Comparative Effectiveness Context:

While Effudex shows similar efficacy to imiquimod in some studies, imiquimod demonstrates superior long-term tumor-free rates (83.4% versus 80.1% at 12 months) and is considered first-line topical therapy by the American Academy of Dermatology. 7, 6 However, the 3-year data shows fluorouracil (68% tumor-free) is comparable to photodynamic therapy (58%) and both are inferior to imiquimod (80%). 3

Common Pitfalls to Avoid

• Do not use Effudex for nodular basal cell carcinoma—it is FDA-approved only for superficial subtypes 1
• Do not rely on clinical appearance to confirm cure—histologic confirmation is essential 4, 2
• Do not use on high-risk facial lesions where surgery would be straightforward, as surgical success approaches 100% 1
• Do not discontinue treatment prematurely due to expected inflammatory reactions unless infection develops 6

Follow-Up Requirements

Schedule follow-up at 3 weeks post-treatment for surgical excision and histologic confirmation, then implement long-term surveillance as 30-50% of patients develop another basal cell carcinoma within 5 years. 4, 2