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Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women

Objective:To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals. Design:Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium. Methods:HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm2 were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD). Results:Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4+ cell count was 412 cells/&mgr;l. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients). Conclusion:Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.