Objectives: To conduct a systematic review to determine clearance rates and adverse effects of topical imiquimod or fluorouracil therapy in the treatment of nonmelanoma skin cancers such as basal (BCC) and squamous cell carcinoma (SCC), and to develop recommendations for the use of topical imiquimod or fluorouracil to treat BCC and SCC.

Data sources: MEDLINE, CANCERLIT, and Cochrane databases.

Study selection: Prospective, retrospective, and case studies in English containing a minimum of 4 subjects and a 6-month follow-up or posttreatment histologic evaluation.

Data extraction: We calculated the rate of clearance and adverse effects for BCC subtypes and invasive and in situ SCC treated with topical imiquimod or fluorouracil.

Data synthesis: Clearance rates varied by drug regimen, and most of the studies lacked long-term follow-up. Imiquimod use produced the following clearance rates: 43% to 100% for superficial BCC, 42% to 100% for nodular BCC, 56% to 63% for infiltrative BCC, 73% to 88% for SCC in situ, and 71% for invasive SCC. Fluorouracil use produced the following clearance rates: 90% for superficial BCC and 27% to 85% for SCC in situ. Up to 100% and 97% of patients applying imiquimod and fluorouracil, respectively, experienced at least 1 adverse event. Adverse event intensity ranged from mild to severe; erythema, pruritus, and pain were common.

Conclusions: Evidence supports the use of topical imiquimod as monotherapy for superficial BCC and topical fluorouracil as monotherapy for superficial BCC and SCC in situ. Based on the available evidence, the strength of any recommendations for the use of these 2 agents in the primary treatment of these tumors is weak. We recommend that their use be limited to patients with small tumors in low-risk locations who will not or cannot undergo treatment with better-established therapies for which long-term clearance rates have been determined. Long-term clinical follow-up is essential for patients treated with topical imiquimod or fluorouracil. Limitations of therapy include high rates of adverse effects, lower clearance rates than other treatment modalities, dependence on patient adherence to treatment, and higher costs than other therapies.