5-Fluorouracil Effective Treatment for CIN 2 in Small Trial

January 02, 2014

Topical 5% 5-fluorouracil (5FU) applied intravaginally may be an effective treatment for cervical intraepithelial neoplasia (CIN) 2 in women, according to a prospective, nonblinded, randomized controlled trial.

Lisa Rahangdale, MD, MPH, assistant professor and medical director of the University of North Carolina Women's Hospital Gynecology Clinic and medical director of the University of North Carolina Women's Hospital Dysplasia Clinic in the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, and colleagues report their findings in an article published online January 2, 2014, in the American Journal of Obstetrics and Gynecology.

"This study provides additional evidence to support pursuit of a feasible topical treatment of CIN," the authors write.

Traditional treatment of CIN 2 and CIN 3 is excisional therapy or ablation of the cervical transformation zone. The disease recurs in 5% to 26% of women, even with negative surgical margins. Excisional treatment increases the risk for premature delivery and is associated with anxiety, pain, bleeding, and healthcare expenditure. Current guidelines recommend close observation of young women as the preferred management strategy for CIN 2 and an acceptable management strategy for CIN 3.

The researchers compared intravaginal 5% 5FU vs standard of-care observation in women aged 18 to 29 years with CIN 2. Those in the treatment group were given intravaginal 5-FU every 2 weeks for a total of 16 weeks, and both groups returned to their provider in 6 months for a Papanicolaou smear, colposcopy, and human papillomavirus (HPV) DNA test.

The primary outcome was disease regression 6 months after CIN 2 diagnosis. Secondary outcomes included high-risk HPV status at 6 months, pathologic findings at 12 months, and safety and acceptability data.

Between August 2010 and June 2013, women were randomly assigned to either the treatment (n = 31) or observation (n = 29) group and underwent a baseline assessment. Of those with cervical biopsy results at 6 months, 93% (26/28) of women in the 5-FU group and 56% (15/27) of those in the observation group met the primary endpoint.

The intention-to-treat analysis found a relative risk (RR) for cervical disease regression of 1.62 (95% confidence interval [CI], 1.10 - 2.56) between the 5-FU and observation groups ( P = .01).

When the researchers combined cervical biopsy, pap smear, and HPV results for the 6-month follow-up visit, half (14/28) of those in the 5FU group had documentation of normal biopsy, normal Papanicolaou smear, and negative HPV test vs 22% (6/27) of those in the observation group (RR, 2.25; 95% CI, 1.05 - 5.09; P < .05).

None of the women in the intervention group reported moderate or severe adverse effects, although 48% of women reported low-grade adverse effects, including pain, discharge, bleeding, and itching or irritation. None of the participants said the adverse effects affected their daily activities.

"[T]opical 5-FU is a readily available, well-tolerated, patient-controlled medical treatment for cervical dysplasia in young women," the authors write. "Though excision and ablation are well-established, standard of care procedures, the time has come for our field to consider and study medical management options as alternatives for women who decline or cannot access surgical treatments," they conclude.

This study was supported by an ACOG Hologic Research Award for the Prevention of Cervical Cancer and the University of North Carolina School of Medicine James W. Woods Junior Faculty Award. Qiagen supplied HPV testing. The authors have disclosed no relevant financial relationships.