Does topical 5-fluorouracil (5-FU) cream prevent skin cancers?

From the Guidelines

Fluorouracil (5-FU) topical cream is effective in reducing the rate of onset of new actinic keratoses (AKs) over a period of 18 months, particularly when applied to a field of involved skin. This is based on a randomized controlled trial that compared a 4-week course of 5-FU, 5% twice daily to a field of involved skin with placebo, as reported in the British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017 1. The guidelines highlight that more active treatment with 5-FU can reduce the rate of onset of new AKs in the treated area.

Some key points to consider when using 5-FU topical cream for the prevention of skin cancers include:

• The typical treatment regimen involves applying 5-FU cream (usually 5% concentration) to affected areas twice daily for 2-4 weeks
• The skin typically becomes red, irritated, and may develop crusting as the medication destroys abnormal cells
• Sun protection remains essential even after treatment is complete, as sunscreen use has been associated with a small decrease in the incidence of squamous cell carcinomas (SCCs) and AKs over a short follow-up period 1
• There are no studies to show that sun avoidance reduces the risk of development of AKs and skin cancer in a population without AKs, but public health campaigns may have an impact on this risk 1

It is essential to note that while 5-FU topical cream is effective in reducing the rate of onset of new AKs, it may not prevent all types of skin cancers, such as basal cell carcinomas (BCCs) 1. However, the available evidence suggests that 5-FU topical cream can be a useful tool in the prevention of skin cancers, particularly in people with a history of AKs or previous skin cancers.

From the FDA Drug Label

INDICATIONS AND USAGE: Fluorouracil Cream USP is recommended for the topical treatment of multiple actinic or solar keratoses. In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. The answer to whether fluorouracil topical cream does anything for the prevention of skin cancers is that the FDA label does not explicitly address prevention. It mentions treatment of actinic or solar keratoses and superficial basal cell carcinomas, but not prevention of skin cancers.

• The label states the cream is for treatment, not prevention.
• Key points are that it is used for treatment of existing lesions, with no mention of preventing new skin cancers from forming. 2

From the Research

Efficacy of Flurouricil Topical Cream in Preventing Skin Cancers

• The use of topical fluorouracil cream has been shown to be effective in treating actinic keratosis, a precancerous condition that can develop into skin cancer 3, 4, 5, 6, 7.
• Studies have demonstrated that topical fluorouracil cream can reduce the number of actinic keratoses and prevent the development of new lesions 6.
• A randomized clinical trial found that a single course of fluorouracil cream, 5%, effectively reduced actinic keratosis counts and the need for spot treatments for longer than 2 years 6.
• Another study found that a novel formulation of 4% 5-fluorouracil cream with once-daily application was highly effective in treating multiple actinic keratoses, with a significant decrease in the Actinic Keratosis Area and Severity Index (AKASI) score at 6 and 12 weeks 7.

Safety and Tolerability of Flurouricil Topical Cream

• Topical fluorouracil cream has been shown to have a satisfactory safety profile, with most adverse reactions being mild and temporary 3, 7.
• A study found that only 10% of patients discontinued therapy due to adverse reactions, and 43% of patients did not report any adverse reactions 7.
• Another study found that the use of 0.5% fluorouracil cream may provide an effective, safe, and economical option for treating actinic keratosis, with less frequent applications improving patient compliance 5.

Comparison with Other Treatment Options

• Topical fluorouracil cream has been compared to other treatment options, such as cryotherapy and immunotherapy, and has been found to be a highly effective treatment for actinic keratosis 4, 7.
• A review of current topical treatment options found that topical fluorouracil cream is one of the most effective and widely prescribed treatments for actinic keratosis 4.