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CROI 2012: Electrocautery Superior to Imiquimod or 5-Fluorouracil for Treatment of Anal Neoplasia

Electrocautery was shown to be more effective and tolerable than topical imiquimod or 5-fluorouracil as a treatment for anal intraepithelial neoplasia (AIN) in HIV positive men who have sex with men (MSM), researchers reported in a late-breaker presentation at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) last week in Seattle.

HIV positive people are more likely than those without HIV to carry oncogenic or cancer-causing types of human papillomavirus (HPV), which can cause abnormal cell changes in the anal-genital region known as dysplasia or intraepithelial neoplasia. High-grade neoplasia can progress to cancer. 

A recent study has shown that as many as 91% of HIV positive MSM will be infected with HPV, with  71% of Pap smears showing dysplasia. As many as 15% of those with untreated high-grade neoplasia develop anal cancer over a 5-year period.

Numerous treatment options exist for HIV positive individuals with anal neoplasia. Among these are surgical excision, ablative treatments using either electrocautery or infrared coagulation, and topical treatment using imiquimod (Aldara) or 5-fluorouracil (Efudex). Despite the variety of therapies available, with imiquimod seeming to be the treatment of choice, no comparative randomized study had been done to determine whether electrocautery would be a better option for this group. 

Olivier Richel from Academic Medical  Center in Amsterdam compared the efficacy of 3 of these treatments. This study included 148 HIV positive MSM with confirmed AIN, 57% of them with high-grade AIN. The average age was about 47 years and they had been infected with HIV for about 9 years. Most were on antiretroviral therapy (ART), about 80% had undetectable viral load, and the current CD4 cell count was about 550 cells/mm3.

Participants were randomized to receive:

• Electrocautery once-monthly for 4 months;
• Imiquimod 3-times-weekly for 16 weeks;
• Topical 5-fluorouracil twice-weekly for 16 weeks.

Participants were evaluated by high-resolution anoscopy, with biopsies 4 weeks and 6 months after the end of treatment.

Results

• In an ITT analysis, complete response, partial response, and total response rates were as follows:
  • Electrocautery: 41%, 7%, and 48%;
  • Imiquimod: 26%, 13%, and 39%;
  • 5-fluorouracil: 17%, 13%, and 30%.
• Recurrence or progression rates 6 months after treatment were 17% for electrocautery, 21% for imiquimod, and 38% for 5-fluorouracil.
• High grade AIN, peri-anal localization, and higher CD4 counts were significantly related to treatment success.
• Electrocautery showed shorter and milder side effects than the topical treatments.
• Severe side effects were seen in 43% of participants on imiquimod and 27% of those on 5-fluorouracil, as opposed to only 18% of those receiving electrocautery.  
• Commonly reported side effects for each treatment included:
  • Electrocautery: bleeding (69%), pain (60%);
  • Imiquimod: pain (70%), bleeding (30%), flu-like symptoms (13%), fatigue (13%);
  • 5-fluorouracil: pain (67%), bleeding (40%), urge (26%), flatulence (15%).

“Electrocautery is more effective than imiquimod and 5-fluorouracil for the treatment of AIN, but all have high recurrence rates,” the researchers concluded. “Electrocautery shows milder and shorter lasting side effects.”

This study showed that despite substantial recurrence rates, electrocautery ablation is superior to both imiquimod and 5-fluorouracil. Richel emphasized that while the side effects for electrocautery lasted only a few days for each of the once-monthly treatments, the side effects of the topical treatments were ongoing for the duration of the 16 weeks due to the frequency of their application.

In a follow-up question Richel stated that while infrared coagulation is similar to electrocautery ablation, it has yet to be determined if it would yield similar results for AIN in this population.

3/16/12

Reference

O Richel, H De Vries, C Van Noesel, et al. Treatment of Anal Intraepithelial Neoplasia in HIV+ MSM: A Triple-arm Randomized Clinical Trial of Imiquimod, Topical 5-Fluoruracil, and Electrocautery. 19th Conference on Retroviruses and Opportunistic Infections. Seattle, March 5-8, 2012. Abstract135LB.