18. Topical 5% 5-flourouracil (t5FU) for treatment of diffuse anal high-grade squamous intraepithelial lesions (aHSIL)

Abstract

Background: Treatment of anal high-grade squamous intraepithelial lesions (aHSIL) may prevent anal cancer. Options for treatment of diffuse lesions include staged ablation, often requiring surgery, although in-office treatment is preferable. Topical 5% 5-fluorouracil (t5FU) has been used to treat diffuse female genital HPV-associated disease. We report our experience using t5FU for treatment of diffuse aHSIL considered unsuitable for ablation, to evaluate its tolerability and efficacy. Methods: Patients were given t5FU for treatment of diffuse aHSIL in doses of 0.5 mL self-applied 2× daily for 5 days followed by 9 days off. Patients were assessed on average following 4–8 cycles for complete response (CR), defined as the absence of HSIL on exam, cytology and/or histology, or partial response (PR), defined as a reduction in the amount of disease. Patients with PR then received ablative therapy. Results: 73 patients (55 HIV infected, 18 uninfected) were treated, including 13 women and 60 men. In 69 patients who used t5FU for at least one cycle, CR occurred in 8 (~11%) patients, 53 (~77%) had a partial response indicating reduction of disease, 6 (9%) had no response, and 1 had more widespread disease, 1 chart was not evaluable. Treatment was discontinued after <1 cycle in 4 patients due to side effects. Patients with PR were treated successfully with in-office ablation, except 2 patients referred for surgery. Conclusions: t5FU was well tolerated although side effects occur. Most patients had clinical improvement, suggesting that t5FU may play an important role in aHSIL treatment. Further studies may determine its optimal use.