Topical Cidofovir and Imiquimod Active in Treating Vulval Intraepithelial Neoplasia
In a UK phase II trial reported in The Lancet Oncology, Tristram et al found that topical cidofovir and topical imiquimod were active in the treatment of vulval intraepithelial neoplasia, suggesting that such treatment may constitute an alternative to surgery.
Study Details
In the open-label study, 180 women aged ≥ 16 years were randomly assigned between October 2009 and January 2013 to cidofovir (n = 89) or imiquimod (n = 91). Cidofovir gel was administered by patients as a thin layer over the affected area three times a week for a maximum of 24 weeks, with every 10-g tube expected to last approximately 6 weeks. Imiquimod patients spread the contents of one sachet (5% imiquimod; 250 mg) over the affected area three times a week for a maximum of 24 weeks. The primary endpoint was histologically confirmed complete response at 6 weeks after the end of treatment.
Response Rates
Complete response was observed in 46% of cidofovir patients (90% confidence interval [CI] = 37.0%–55.3%) and 46% of imiquimod patients (90% CI = 37.2%–55.3%). Adherence to the regimens at treatment week 6 was 88% and 86%. Early stopping of treatment due to achievement of complete response by 18 weeks occurred in 11% of the cidofovir group and 20% of the imiquimod group. Follow-up data for the 83 patients with complete response are not mature; however, 20 (87%) of 23 cidofovir patients and 25 (78%) of 32 imiquimod patients still had complete response at 12 months.
Adverse Events
Treatment was stopped early due to intolerance in 11% of the cidfovoir group and 17% of the imiquimod group. The most common grade 1 or 2 adverse events were pruritus (70% and 74%) and vulval pain (58% and 68%).
Adverse events of grade ≥ 3 occurred in 37% and 46%, with the most common being vulval pain (19% and 15%), pruritus (13% and 12%), fatigue (15% and 27%), and headache (4% and 12%). No grade 4 adverse events were observed in the cidofovir group; grade 4 events in the imiquimod group consisted of fatigue in 4%, vulval pain in 1%, and headache in 1%.
The investigators concluded: “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 effective alternatives to surgery for female patients with vulval intraepithelial neoplasia after exclusion of occult invasive disease.”
Christopher N. Hurt, MSc, of Cardiff University School of Medicine, is the corresponding author for the Lancet Oncology article.
The study was funded by Cancer Research UK. Gareth Griffiths, PhD, has received grants from Pfizer and has acted as a statistical consultant to Pfizer.
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