5-FU Effectively Treats Vaginal Intraepithelial Neoplasia

Ricki Lewis, PhD

November 08, 2017

The topical chemotherapeutic drug 5-fluorouracil (5-FU) was more effective at treating high-grade vaginal intraepithelial neoplasia (VIN) than surgical excision or laser ablation, according to results of a study published in the December issue of Obstetrics & Gynecology.

VIN is an uncommon precancerous condition, with most cases linked to human papillomavirus (HPV) infection. Low-grade lesions may spontaneously resolve. High-grade lesions are treated with hormone therapy, topical preparations, surgical excision, heat or laser ablation, or radiation. Topical 5-FU (5% concentration) is often prescribed off-label to treat VIN.

Stephen Fiascone, MD, from Brigham and Women's Hospital, Boston, Massachusetts, and colleagues conducted a nonrandomized, retrospective case series study to compare the efficacy of 5-FU, surgical excision, and laser ablation and to evaluate use of 5-FU to treat recurrent or persistent high-grade VIN. The condition has a recurrence risk for 43% after surgical excision, the authors note.

Patients were treated between April 1994 and May 2016 at one of two centers in Boston. The researchers used the health records to obtain information on demographic characteristics, HPV risk factors and vaccine status, Pap test findings, history of vulvar and cervical dysplasia, and treatment outcomes. The women had been referred for colposcopy after an abnormal HPV test, cervical cytology findings, or presence of lesions.

Specifically, women had a first-time, biopsy-proven diagnosis of VIN 2, 3, or 2 to 3; high-grade VIN; or a squamous intraepithelial lesion suspicious for but not diagnostic of high-grade VIN. Initial treatment was 5-FU, excision, or laser ablation.

Participants were counseled on all treatments. Those opting for 5-FU treated themselves once weekly for 8 weeks and were followed up 4 weeks after the last dose with a Pap test. If VIN had not resolved, patients were offered surgical excision (particularly for unifocal lesions that appeared more likely to be cancerous) or laser ablation. If lesions resolved after initial treatment but reappeared, the patient was offered 5-FU again.

The analysis included 104 patients, 47 of whom were initially treated with 5-FU, 35 with excision, and 22 with laser ablation. Forty (38%) of the women developed recurrent or persistent VIN.

Among the 47 patients who initially received 5-FU, 35 (74%) remained recurrence free after a median follow-up of 18 months (range, 4 - 92 months). Among the 35 women treated initially with excision, 20 (57%) had no recurrence or persistence after a median follow-up of 38 months (range, 1 - 129 months), and among the 22 women treated initially with laser ablation, nine (41%) had no recurrence or persistence after a median follow-up of 65.5 months (range, 7 - 240 months).

Of the 40 patients who developed recurrent or persistent VIN after the initial treatment, 13 then received 5-FU. Eight (62%) of them did not develop further neoplasia. Of the remaining five women, after a mean follow-up of 18.9 months, four still had high-grade VIN but none had progressed to cancer.

Overall, among the 47 women who received 5-FU as the first line treatment, only nine (19%) eventually had surgical excision or laser ablation.

Nine (16%) of 58 patients who received 5-FU either as frontline treatment or after excision or ablation reported an adverse effect, which was most often irritation or dyspareunia.

"5-fluorouracil was associated with a 74% success rate as the initial treatment modality for high-grade vaginal dysplasia," the researchers conclude; they also note there is a role for the treatment of recurrent or persistent high-grade VIN.

They add that excision introduces surgical risks and ablation can damage tissue, interfering with histology-based diagnosis. "Given these risks, a topical treatment with well-established efficacy and safety would clearly have a role in the management of high-grade vaginal intraepithelial neoplasia," they write.

In a journal podcast, Nancy C. Chescheir, MD, from the University of North Carolina at Chapel Hill School of Medicine, and editor-in-chief of Obstetrics & Gynecology, said the data were reassuring because recurrence risks were similar in all three treatment groups. But she pointed out that a limitation of the study was that follow-up times differed among the three groups, especially given the uptick in 5-FU use during the last 5 years. She said she would like to see data in 4 or 5 years to confirm 5-FU's lead in efficacy.

"I think they've provided some really good information that supports the off-label use of this drug as first-line therapy and as second-line therapy for women who failed any of the treatments. Most women would much prefer a medical therapy that has some side effects that occur in less than 1 in 5 patients and that go away once you're off the drug. So overall this is great news," Dr Chescheir said.

The authors and commentator have disclosed no relevant financial relationships.

Obstet Gynecol. 2017;130:1237-1243.

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