Topical treatment of CIN 2+ by cidofovir: Results of a phase II, double-blind, prospective, placebo-controlled study

Pachterbeke, C. Van; Bucella, Dario; Rozenberg, Serge; Manigart, Yannick; Gilles, Christine; Larsimont, Denis; Houte, Katherina Vanden; Reynders, Marijke; Snoeck, Robert; Bossens, Michel

doi:10.1016/j.ygyno.2009.06.042

Cited by 59 publications

(52 citation statements)

References 24 publications

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“…Several reports have highlighted the efficacy of CDV against HPV-associated malignancies, including hypopharyngeal and esophageal (Van Cutsem et al, 1995), gingival and oral neoplasias (Collette and Zechel, 2011) as well as several anogenital neoplasias such as cervical Van Pachterbeke et al, 2009), vulvar (Koonsaeng et al, 2001;Tristram and Fiander, 2005;Stier et al, 2013), and perianal intraepithelial neoplasias . It should be noted that in the neoplasias successfully treated with CDV, no viral productive infection is detected and only a limited number of viral genes are expressed.…”

Section: In Vitro In Vivo and Clinical Evidences For The Anti-papillmentioning

confidence: 99%

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

et al. 2015

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Acyclic nucleoside phosphonates (ANPs) are well-known for their antiviral properties, three of them being approved for the treatment of human immunodeficiency virus infection (tenofovir), chronic hepatitis B (tenofovir and adefovir) or human cytomegalovirus retinitis (cidofovir). In addition, cidofovir is mostly used off-label for the treatment of infections caused by several DNA viruses other than cytomegalovirus, including papilloma- and polyomaviruses, which do not encode their own DNA polymerases. There is considerable interest in understanding why cidofovir is effective against these small DNA tumor viruses. Considering that papilloma- and polyomaviruses cause diseases associated either with productive infection (characterized by high production of infectious virus) or transformation (where only a limited number of viral proteins are expressed without synthesis of viral particles), it can be envisaged that cidofovir may act as antiviral and/or antiproliferative agent. The aim of this review is to discuss the advances in recent years in understanding the mode of action of ANPs as antiproliferative agents, given the fact that current data suggest that their use can be extended to the treatment of non-viral related malignancies.

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Section: In Vitro In Vivo and Clinical Evidences For The Anti-papillmentioning

confidence: 99%

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

et al. 2015

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“…This agent has been used in patients with either laryngeal, esophageal/pharyngeal or genital HPV-induced proliferative lesions with promising results [128]. In cervical preinvasive disease (biopsy-proven cervical intraepithelial neoplasia-2+), a double-blind randomized Phase II study of topical cidofovir or placebo that allocated 23 patients to cidofovir and 25 to placebo, viral clearance was statistically higher in the active than placebo group (60.8 vs 20%, p < 0.01), suggesting its potential use for this condition [129]. Despite the strong rationale of using anti-HPV targeted agents, the clinical development of these agents is quite limited.…”

Section: Hpv-targeted Therapymentioning

confidence: 99%

Emerging drugs for the treatment of cervical cancer

Serrano-Olvera

Cetina

Coronel

et al. 2015

Expert Opinion on Emerging Drugs

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Concurrent cisplatin with radiation and lately, gemcitabine-cisplatin chemoradiation has resulted in small but significant improvements in the treatment of locally advanced and high-risk early-stage patients. So far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and encouraging results in a Phase II study. In advanced disease, cisplatin doublets yield median survival rates not exceeding 14 months. The first Phase III study of bevacizumab, added to standard chemotherapy cisplatin- or non-cisplatin-containing doublet, has shown significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. The characterization of the mutational landscape of CC and developments of novel targeted therapies may result in more effective and individualized treatments for CC. The potential efficacy of knocking down the key alterations in CC, E6 and E7 human papilloma virus oncoproteins must not be overlooked.

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“…It has also been used to treat HR-HPV related cervical dysplasia 21 and more recently with some success where 14/23 (>60%) of women with pre-treatment biopsy confirmed CIN2 were found to be histologically normal following 3 physician-applied local applications of cidofovir 22 . However, since this drug is both mutagenic 23 and carcinogenic in animals its use for the treatment of HPV related benign and pre-malignant pathologies has proved controversial 24 .…”

Section: Cidofovirmentioning

confidence: 99%

An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia

Hampson

Martin-Hirsch

Hampson

2015

Expert Opinion on Investigational Drugs

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Introduction: Infection with hHigh-risk types of HPV (HR-HPV) isare the main aetiological agent forcause of invasive cervical cancer (ICC) from which there are >270,000 deaths per annum world-wide with over 85% of these occurring in lowresource countries. Ablative and excisional treatment modalities are restricted for use with high-grade pre-cancerous cervical disease with HPV infection and low-grade dysplasia is currently managed by a watch-and-wait policy.

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Topical treatment of CIN 2+ by cidofovir: Results of a phase II, double-blind, prospective, placebo-controlled study

Cited by 59 publications

References 24 publications

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

Emerging drugs for the treatment of cervical cancer

An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia

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