Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia.

OBJECTIVES

To investigate the activity of 5% Imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3.

METHODS

Patients with histologically confirmed VIN 2/3 were recruited from regional colposcopy units. A Simon two-stage phase 2 study design was used. Imiquimod cream was applied over the abnormal VIN areas by the patients, using an escalating dose regimen for a total treatment duration of 16 weeks. Colposcopy assessments were performed every 2 weeks to evaluate for response. A historical cohort of VIN 2/3 patients treated with primary surgical ablation was used to compare recurrence patterns.

RESULTS

Thirty-nine patients enrolled in the study. Six patients dropped out due to side effects and non-compliance with study protocol. Thirty-six patients (92%) had VIN 3. Therapy was well tolerated with the most common observed side effects being only minor skin irritation at the application site. Histologic complete response was observed in 21 patients with partial response in another nine patients. The overall response rate was 77% using intention to treat principle. No VIN progression or cancer was diagnosed. At a median follow-up of 16 months in the whole study cohort, eight recurrences (20.5%) were observed. In comparison, the recurrence rate for primary surgically treated patients was 53.5% (p=0.013).

CONCLUSION

Imiquimod cream was well tolerated and resulted in the regression in a majority of high-grade VIN lesions. The recurrence rate appeared to be comparable to primary surgical ablation.