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

Elizabeth A. Stier, Stephen E. Goldstone, Mark Einstein, Naomi Jay, John M. Berry, Timothy Wilkin, Jeannette Y. Lee, Teresa M. Darragh, Maria Da Costa, Lori Panther, David Aboulafia, Joel M. Palefsky

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. 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 3cm 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 412cells/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). 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.

Original languageEnglish (US)
Pages (from-to)545-551
Number of pages7
JournalAIDS
Volume27
Issue number4
DOIs
StatePublished - Feb 20 2013

Fingerprint

HIV
Safety
Neoplasms
cidofovir
Biopsy
Therapeutics
CD4 Lymphocyte Count
Clinical Protocols
Multicenter Studies
Acquired Immunodeficiency Syndrome
Pain
Polymerase Chain Reaction
Skin
DNA

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

Keywords

  • Bowen's disease
  • HIV
  • cidofovir
  • human papillomavirus
  • perianal intraepithelial neoplasia
  • vulvar intraepithelial neoplasia

Cite this

Stier, Elizabeth A. ; Goldstone, Stephen E. ; Einstein, Mark ; Jay, Naomi ; Berry, John M. ; Wilkin, Timothy ; Lee, Jeannette Y. ; Darragh, Teresa M. ; Da Costa, Maria ; Panther, Lori ; Aboulafia, David ; Palefsky, Joel M. / Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. In: AIDS. 2013 ; Vol. 27, No. 4. pp. 545-551.
@article{4e5cc5b7ce7c42a58fe0f36bbf83ea1a,
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. 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 3cm 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 412cells/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). 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.",
keywords = "Bowen's disease, HIV, cidofovir, human papillomavirus, perianal intraepithelial neoplasia, vulvar intraepithelial neoplasia",
author = "Stier, {Elizabeth A.} and Goldstone, {Stephen E.} and Mark Einstein and Naomi Jay and Berry, {John M.} and Timothy Wilkin and Lee, {Jeannette Y.} and Darragh, {Teresa M.} and {Da Costa}, Maria and Lori Panther and David Aboulafia and Palefsky, {Joel M.}",
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Stier, EA, Goldstone, SE, Einstein, M, Jay, N, Berry, JM, Wilkin, T, Lee, JY, Darragh, TM, Da Costa, M, Panther, L, Aboulafia, D & Palefsky, JM 2013, 'Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women', AIDS, vol. 27, no. 4, pp. 545-551. https://doi.org/10.1097/QAD.0b013e32835a9b16

Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. / Stier, Elizabeth A.; Goldstone, Stephen E.; Einstein, Mark; Jay, Naomi; Berry, John M.; Wilkin, Timothy; Lee, Jeannette Y.; Darragh, Teresa M.; Da Costa, Maria; Panther, Lori; Aboulafia, David; Palefsky, Joel M.

In: AIDS, Vol. 27, No. 4, 20.02.2013, p. 545-551.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Safety and efficacy of topical cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women

AU - Stier, Elizabeth A.

AU - Goldstone, Stephen E.

AU - Einstein, Mark

AU - Jay, Naomi

AU - Berry, John M.

AU - Wilkin, Timothy

AU - Lee, Jeannette Y.

AU - Darragh, Teresa M.

AU - Da Costa, Maria

AU - Panther, Lori

AU - Aboulafia, David

AU - Palefsky, Joel M.

PY - 2013/2/20

Y1 - 2013/2/20

N2 - 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 3cm 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 412cells/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). 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.

AB - 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 3cm 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 412cells/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). 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.

KW - Bowen's disease

KW - HIV

KW - cidofovir

KW - human papillomavirus

KW - perianal intraepithelial neoplasia

KW - vulvar intraepithelial neoplasia

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