title: Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women.
abstract: 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.
  
  
  METHODS
  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 cm 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/μl. 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Boston University Medical Center, Boston, MA, USA. elstier@bmc.org
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stier
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Goldstone
authors.forename: Mark H
authors.initials: MH
authors.lastname: Einstein
authors.forename: Naomi
authors.initials: N
authors.lastname: Jay
authors.forename: John M
authors.initials: JM
authors.lastname: Berry
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilkin
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Darragh
authors.forename: Maria
authors.initials: M
authors.lastname: Da Costa
authors.forename: Lori
authors.initials: L
authors.lastname: Panther
authors.forename: David
authors.initials: D
authors.lastname: Aboulafia
authors.forename: Joel M
authors.initials: JM
authors.lastname: Palefsky
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018791:CD4 Lymphocyte Count; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology; D000077404:Cidofovir; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D010502:Perineum / Q000473:pathology*; D011446:Prospective Studies; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000998:Antiviral Agents; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir