Safety and tolerance of cidofovir as a 2% gel for local application in high-grade cervical intraepithelial neoplasia: A phase 1 investigation.

OBJECTIVES: The primary objective was to evaluate the safety and local tolerance of a topical 2% (w/w) cidofovir gel, applied directly to the cervices of women with high-grade cervical intraepithelial neoplasia (CIN 2+). The secondary objective was to evaluate the pharmacokinetics of cidofovir during the treatment. MATERIALS AND METHODS: Nine women with CIN 2+, were treated with a course of 3 g of cidofovir gel, applied locally once per week for 3 weeks in total (9 g). The treatment was administered in a cervical cap, applied to the cervix for 5 or 10 hours (n = 6 and 3 patients, respectively). Follow-up included a structured questionnaire, a gynecological examination, blood analysis for hematology, C-reactive protein (CRP), and renal function assessment plus pharmacokinetic analyses of cidofovir after each treatment and at the end of the full course. RESULTS: No clinically significant hematological/biochemical abnormalities or serious adverse events (SAE) were reported, although 6 mild to moderate adverse events (AE) occurred in relation to the study drug: 1 flu-like syndrome and 5 local AEs. Plasma concentrations of cidofovir were very low (mean Cmax of 103.0 and 99.2 ng/mL after 5 and 10 hours of exposure, respectively). CONCLUSION: Cidofovir, directly applied on CIN 2+, is reasonably well tolerated and the systemic exposure following topical application is much lower than that seen with intravenous administration, at the approved dose..