Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT³VIN): a multicentre, open-label, randomised, phase 2 trial

Tristram, Amanda, Hurt, Christopher N. ORCID: https://orcid.org/0000-0003-1206-8355, Madden, Tracie ORCID: https://orcid.org/0000-0001-7880-7873, Powell, Ned, Man, Stephen ORCID: https://orcid.org/0000-0001-9103-1686, Hibbitts, Sam, Dutton, Peter, Jones, Sadie, Nordin, Andrew J., Naik, Raj, Fiander, Alison and Griffiths, Gareth 2014. Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT³VIN): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncology 15 (12) , pp. 1361-1368. 10.1016/S1470-2045(14)70456-5

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Abstract

Summary Background Vulval intraepithelial neoplasia is a skin disorder aff ecting the vulva that, if left untreated, can become cancerous. Currently, the standard treatment for patients with vulval intraepithelial neoplasia is surgery, but this approach does not guarantee cure and can be disfi guring, causing physical and psychological problems, particularly in women of reproductive age. We aimed to assess the activity, safety, and feasibility of two topical treatments— cidofovir and imiquimod—as an alternative to surgery in female patients with vulval intraepithelial neoplasia. Methods We recruited female patients (age 16 years or older) from 32 centres to an open-label, randomised, phase 2 trial. Eligibility criteria were biopsy-proven vulval intraepithelial neoplasia grade 3 and at least one lesion that could be measured accurately. We randomly allocated patients to topical treatment with either 1% cidofovir (supplied as a gel in a 10 g tube, to last 6 weeks) or 5% imiquimod (one 250 mg sachet for every application), to be self-applied three times a week for a maximum of 24 weeks. Randomisation (1:1) was done by stratifi ed minimisation via a central computerised system, with stratifi cation by hospital, disease focality, and presentation stage. The primary endpoint was a histologically confi rmed complete response at the post-treatment assessment visit 6 weeks after the end of treatment (a maximum of 30 weeks after treatment started). Analysis of the primary endpoint was by intention to treat. Secondary outcomes were toxic eff ects (to assess safety) and adherence to treatment (to assess feasibility). We present results after all patients had reached the primary endpoint assessment point at 6 weeks; 2-year follow-up of complete responders continues. This trial is registered with Current Controlled Trials, ISRCTN 34420460. Findings Between Oct 21, 2009, and Jan 11, 2013, 180 participants were enrolled to the study; 89 patients were randomly allocated cidofovir and 91 were assigned imiquimod. At the post-treatment assessment visit, a complete response had been achieved by 41 (46%; 90% CI 37·0–55·3) patients allocated cidofovir and by 42 (46%; 37·2–55·3) patients assigned imiquimod. After 6 weeks of treatment, 156 (87%) patients (78 in each group) had adhered to the treatment regimen. Five patients in the cidofovir group and seven in the imiquimod group either withdrew or were lost to follow-up before the fi rst 6-week safety assessment. Adverse events of grade 3 or higher were reported in 31 (37%) of 84 patients allocated cidofovir and 39 (46%) of 84 patients assigned imiquimod; the most frequent grade 3 and 4 events were pain in the vulva, pruritus, fatigue, and headache. Interpretation Cidofovir and imiquimod were active, safe, and feasible for treatment of vulval intraepithelial neoplasia and warrant further investigation in a phase 3 setting. Both drugs are eff ective alternatives to surgery for female patients with vulval intraepithelial neoplasia after exclusion of occult invasive disease. Funding Cancer Research UK.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information:	Open Access article distributed under the terms of CC BY.
Publisher:	Elsevier: Lancet
ISSN:	1470-2045
Funders:	Cancer Research UK
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	2 October 2014
Last Modified:	21 Oct 2023 01:08
URI:	https://orca.cardiff.ac.uk/id/eprint/65657

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