Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study. Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia.
To investigate the effect of topical imiquimod in patients with vulvar intraepithelial neoplasia (VIN).
                We used a prospective, randomised, double-blinded, placebo-controlled study. Women with biopsy verified, visible VIN2 or VIN3, in a biopsy not older than 2 months were considered.
                Thirty-two patients were included, one was excluded before treatment. Twenty-one received active treatment, 10 received placebo. Seventeen (81%) in the treatment group showed complete response, two (10%) partial response and none responded in the placebo-group when evaluated by a biopsy 2 months after a treatment period of 16 weeks. Fourteen of 21 patients (67%) in the treatment group had to reduce the number of applications due to local side-effects.
                The topical treatment with imiquimod 5% was shown in this setting to be very efficient. Local side effects were a common feature, but tolerable after dose reduction. Long-term results are not known, but a planned cohort study of this population will show the rate of recurrences. Recently we reported on the efficacy of imiquimod for treating vulvar intraepithelial neoplasia (VIN) in a placebo-controlled, double-blinded randomized clinical trial (RCT). Four weeks after treatment, a complete response was observed in 35% of patients and a partial response in 46%. All complete responders remained disease-free at 12 months follow-up. In the current investigations, we assessed long-term follow-up at least 5 years after the initial RCT.
                Twenty-four of 26 imiquimod-treated patients who had participated in the initial RCT were seen for follow-up. Primary endpoint was durability of clinical response to imiquimod assessed by naked eye vulvar examination and histology. Long-term clinical response was correlated to lesion size before start of the initial RCT. Secondary endpoints were mental health, global quality of life, body image and sexual function in relation with long-term clinical response.
                Median follow-up period was 7.2 years (range 5.6-8.3 years). VIN recurred in one of nine complete responders. Of the initial partial responders, two became disease-free after additional imiquimod treatment. In the other partial responders, VIN recurred at least once after the initial RCT. In long-term complete responders, lesion size at study entry was smaller and these patients had a significantly better global quality of life at follow-up than patients with residual disease and/or recurrence after imiquimod treatment.
                In case of a complete response, imiquimod is effective in the long-term. Furthermore, patients with a long-term complete response had a significantly better global quality of life than patients who recurred after imiquimod treatment.
                Copyright © 2010 Elsevier Inc. All rights reserved. The aim of this study was to determine the potential therapeutic benefits of indole-3-carbinol (I3C) in the management of vulvar intraepithelial neoplasia (VIN). Women with histologically confirmed high-grade VIN were randomized to receive 200 and 400 mg/day of I3C. Symptomatology by visual analog scale and vulvoscopic appearance were assessed at recruitment, 6 weeks, 3 months, and 6 months. Tissue biopsy to determine histologic response was obtained at completion of the study period. Urine samples were obtained at each visit to determine 2-hydroxyestrone to 16-alpha-hydroxyestrone ratios. Data from 12 women were suitable for analysis. There was a significant improvement in symptomatology with the introduction of I3C (itch, P= 0.018; pain, P= 0.028). Lesion size and severity were also significantly reduced (size, P= 0.005; appearance, P= 0.046). In addition, there was a significant increase in 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio following commencement of I3C, P= 0.05. However, tissue biopsy from the worst-affected vulval areas revealed no improvement in grade of VIN during the 6-month period, P= 0.317. There were no significant differences in results between those women taking 200 mg/day of I3C and those on 400 mg/day. This study has shown significant clinical improvement in symptomatology and vulvoscopic appearance of VIN with I3C therapy. Further clinical and scientific investigations are required to support these preliminary findings.
Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.