The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for squamous cell skin cancer recommend 5-fluorouracil (5-FU)-based regimens as the preferred therapy for field cancerization or confluent epidermal dysplasia, with a specific emphasis on the use of topical 5-FU. For systemic therapy alone, a combination of cisplatin and 5-FU is considered useful in some circumstances. Similarly, the most recent NCCN guidelines for basal cell skin cancer do not specifically mention intralesional administration of 5-FU. Topical 5-FU is considered useful in certain circumstances as a primary treatment for low-risk patients. However, the use of other routes of administration is not explicitly discussed. [1], [2]
A 2024 review synthesized data from 47 studies evaluating the clinical efficacy and safety of 5-FU and bleomycin in dermatology. The review detailed both intralesional and topical formulations of these agents, with mechanisms rooted in inhibition of DNA synthesis and induction of apoptosis. Bleomycin was noted to be particularly effective in treating hypertrophic scars and warts, demonstrating advantages over 5-FU in some cases. However, 5-FU, due to its lower cost and reduced injection-related pain, emerged as a viable alternative, especially in combination therapies. Notable findings also included the potential of intralesional bleomycin or 5-FU for non-surgical management of cutaneous malignancies in patients unfit for surgery; intralesional 5-FU may be attempted for actinic keratosis when 5-FU cream is unavailable, and there are scattered reports of intralesional 5-FU administration in basal cell carcinoma (BCC) and keratoacanthoma. Despite these advancements, the authors noted the need for further research given the limited contemporary data. [3]
A 2015 review assessed the use of intralesional 5-FU as an alternative treatment for nonmelanoma skin cancer (NMSC), including BCC, squamous cell carcinoma (SCC), and keratoacanthoma. The review evaluated 12 studies encompassing both retrospective case series and prospective trials, focusing on the efficacy, dosing regimens, and adverse effects of intralesional 5-FU. Use of 5-FU produced promising outcomes, particularly for less aggressive histological types of BCC and keratoacanthoma, with efficacy rates ranging from 79% to 100% for BCC and 97% for keratoacanthoma. Despite limited data for SCC, high clearance rates (up to 96%) were noted in small sample sizes. The most common dosing involved 0.5 to 2 mL injections of 50 mg/mL aqueous 5-FU administered weekly or biweekly, typically requiring 4 to 8 treatments for clinical resolution. Local adverse events, including erythema, ulceration, and transient hyperpigmentation, were frequent but minor, with no systemic toxicities reported. However, scarring was observed as a cosmetic side effect in some cases. The findings suggest that intralesional 5-FU may offer a viable nonsurgical option for NMSC, warranting further research to optimize dosing and reduce treatment frequency while maintaining safety and efficacy. [4]
A 2023 case series explored the use of dilute intralesional 5-FU for treating NMSC, specifically SCC and keratoacanthomas. The study involved 11 patients who received intralesional 5-FU at concentrations of 10.0 mg/mL and 16.7 mg/mL for 40 squamous cell carcinomas and 10 keratoacanthomas. The results showed that dilute intralesional 5-FU successfully treated 96% of the lesions, with complete clinical clearance achieved in 9 patients (82%) over a mean follow-up period of 21.7 months. No adverse effects or local recurrences were reported, suggesting that more dilute preparations of 5-FU may reduce cumulative dose and dose-dependent side effects while maintaining effectiveness. However, caution is warranted in interpretation as only the abstract was available for scrutiny, limiting a full analysis of the findings. [5]