What is the treatment for basal cell carcinoma with Efudex (fluorouracil)?

Treatment of Basal Cell Carcinoma with Efudex (5-Fluorouracil)

Efudex (5% fluorouracil cream) is FDA-approved for superficial basal cell carcinomas but should only be used when conventional surgical methods are impractical, such as with multiple lesions or difficult treatment sites, as it has a lower cure rate (~93%) compared to surgery (nearly 100%). 1

When to Consider Efudex for BCC

Efudex is reserved for non-surgical candidates only, as surgical approaches remain the gold standard with superior cure rates. 2 The American Academy of Dermatology guidelines emphasize that nonsurgical therapies like 5-FU should be considered only when surgery or radiation therapy is contraindicated or impractical, with the understanding that cure rates may be lower. 3

Appropriate Clinical Scenarios:

• Superficial BCC only (not nodular or infiltrative subtypes) 1
• Multiple lesions where surgery would be impractical 1
• Difficult anatomic sites where surgery poses challenges 1
• Low-risk tumors in patients who refuse or cannot tolerate surgery 3

Contraindications:

• Nodular or infiltrative BCC - Efudex has not been proven effective for these aggressive subtypes 1
• Isolated, easily accessible lesions where surgery would achieve nearly 100% cure 1
• High-risk features (large size ≥2 cm, poorly defined borders, recurrent tumors, facial location, perineural invasion) 2

FDA-Approved Treatment Protocol

Apply 5% fluorouracil cream twice daily in an amount sufficient to cover the lesions for at least 3 to 6 weeks, with therapy potentially required for as long as 10 to 12 weeks before lesions are obliterated. 1 The medication should be applied preferably with a non-metal applicator or suitable glove, and hands must be washed immediately if applied with fingers. 1

Expected Response Sequence:

• Erythema (redness) 1
• Vesiculation (blistering) 1
• Desquamation (peeling) 1
• Erosion 1
• Re-epithelialization (healing) 1

Efficacy Data

The FDA label reports approximately 93% cure rate based on 113 lesions in 54 patients (88 lesions treated produced 7 failures). 1 However, this is notably lower than surgical cure rates approaching 100%. 1

Recent research supports these findings:

• A 2007 study showed 90% histologic cure rate (28/31 lesions) for superficial BCC on trunk or limbs with mean treatment time of 10.5 weeks 4
• A 2000 pilot study using phosphatidyl choline as a carrier showed 90% cure rate (9/10 lesions) versus 57% (4/7) with standard petrolatum-based formulation 5

Important caveat: The NCCN guidelines note that topical 5-FU has been shown in randomized trials to have similar efficacy to imiquimod for superficial BCC, but both have lower cure rates than surgical options. 3

Critical Follow-Up Requirements

The diagnosis must be established by biopsy prior to treatment, and patients must be followed for a reasonable period to determine if cure has been obtained, as this is a neoplastic condition. 1 This is non-negotiable because:

• Clinical appearance alone is insufficient to confirm clearance 1
• Histologic confirmation of cure is essential 4
• 30-50% of BCC patients develop another BCC within 5 years 2

Comparative Effectiveness

When comparing 5-FU to other nonsurgical options for superficial BCC:

• Photodynamic therapy (PDT): British guidelines show 5-FU had 83% complete response at 3 months versus 93% with MAL-PDT, but only 48% of 5-FU patients remained clear at 12 months versus 82% with PDT 3
• Imiquimod: NCCN data shows similar efficacy between 5-FU and imiquimod for superficial BCC 3
• Cryotherapy: Recurrence rates for cryotherapy range from 6.3% to 39%, making it generally less favorable 3

Common Pitfalls to Avoid

• Do not use for nodular BCC on face or neck except under unusual circumstances with mandatory histologic follow-up 6
• Avoid periocular application to prevent corneal toxicity 7
• Do not assume clinical clearance equals histologic cure - excisional biopsy 3 weeks after treatment completion is recommended 4
• Recognize that treatment duration may extend to 12 weeks - premature discontinuation reduces efficacy 1, 4
• Monitor for complications: primary irritant dermatitis and allergic contact dermatitis must be recognized promptly 6

Tolerability Profile

5-FU is generally well tolerated with good cosmetic outcomes. 4 Most patients experience:

• Mild to moderate erythema 4
• Minimal pain 4
• No scarring 4
• High patient satisfaction 4

The British guidelines note that moderate-to-severe local adverse events include skin redness, swelling, erosions, crusts, vesicles, and itching, which may vary greatly in severity and potentially limit compliance. 3

Chemoprevention Consideration

A 2018 Veterans Affairs trial demonstrated that a single 2-4 week course of 5% fluorouracil to the face and ears produced a 75% reduction in squamous cell carcinoma risk during the first year (1% vs 4%, P=0.002), though the 11% reduction in BCC risk was not statistically significant. 8 This suggests potential value for field cancerization in high-risk patients, though this is distinct from treating established BCC.