BERNALILLO, N.M. – Intravaginal 5-fluorouracil might be a better option than watchful waiting for women with stage II cervical intraepithelial neoplasia, according to a small trial from the University of North Carolina at Chapel Hill.
Twenty-eight women aged 18-29 years with CIN 2 self-administered 2 g of 5% 5-fluorouracil cream (5-FU) intravaginally by applicator every 2 weeks for 16 weeks; 28 others were randomized to observation, the usual approach.
Dr. Lisa Rahangdale
At 6 months, disease had regressed on colposcopic biopsy in 96% (27) of the 5-FU women, and 56% (15/27) were free of cervical human papilloma virus (HPV). Disease regressed in 57% (16) of the control group, and just 26% (7/27) were free of cervical HPV. The findings were statistically significant.
"The results from this study indicate that 5-FU is an effective medical therapy for CIN 2 in young women whose disease is being observed at 6-month intervals. Further investigation in women who are older or with a CIN 3 diagnosis is needed prior to considering this option in lieu of excisional or ablative management strategies," said lead investigator Dr. Lisa Rahangdale of the department of obstetrics and gynecology at the university.
"We need more data to make this a standard of care recommendation, but it has been successful in my practice," she said.
So long as they agree to avoid pregnancy while on the category X drug, "I’ve started offering women this option, particularly if they are not interested in an excisional procedure and are planning on childbearing; they are really excited to have a nonsurgical option. I also use it for women" with positive margins after excision, Dr. Rahangdale said. "Based on [a] previous study of HIV-positive women, this will help reduce their recurrence of disease," she added (Obstet. Gynecol. 1999;94:954-61).
About half of the women in the trial reported side effects, including irritation, discharge, and intermenstrual bleeding. One woman was withdrawn for possible ulceration; another, for vulvar erythema.
Even so, the women said the side effects didn’t interfere with their lives, and most would recommend 5-FU to a friend.
Topical formulations of the old chemotherapy drug were used in the past for genital warts and other HPV problems, but the drug was largely abandoned because of significant side effects with multiple doses per week. "I think our side effect profile is relatively favorable" because the dosing is biweekly, Dr. Rahangdale said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
Most of the study subjects were white, and there were no statistically-significant between-group differences in HPV vaccination history, history of prior dysplasia, contraception or condom use, number of sexual partners, and other parameters. About a third of the treated women and a fifth of the untreated women reported having had at least one dose of HPV vaccine.
Dr. Rahangdale said she had no relevant financial disclosures.