Sep 14, 2010
Can a chemo cream help prevent anal cancer?
Researchers in Germany and the Netherlands have tested a cream formulation of an anti-cancer drug (Efudex, 5-FU, fluorouracil) against precancerous anal lesions in HIV-positive men. 5-FU was inserted a short distance into the anal canal. This drug was associated with a significant clearance of precancerous anal lesions and other abnormal anal growths. However, recurrence of anal lesions was common, as were side effects.
Researchers recruited 46 HIV-positive men, all who had biopsy-confirmed intra-anal lesions caused by human papillomavirus (HPV) infection. All the men had their anuses inspected with high-resolution anoscopy and those with abnormal growths received 5-FU formulated as a cream. Participants applied about one gram of the cream intra-anally twice weekly at night for 16 weeks. The men had their anuses monitored by study personnel every four to eight weeks over the course of 20 weeks.
If side effects related to 5-FU occurred (burning, pain, soreness, urge to defecate) and they were mild, participants could reduce therapy to once-weekly dosing. In cases where side effects were stronger, participants could interrupt therapy for a week.
The average profile of the 46 participants was as follows:
- age – 46 years
- CD4+ count – 526 cells
- 89% were taking anti-HIV therapy
- 83% had a viral load less than 40 copies/ml
- 76% had two or more lesions in their anus
- in 17 of the 46 men, the lesions were highly abnormal (i.e., pre-cancerous)
- complete responders (all lesions cleared) – 39%
- partial responders (lesions became less abnormal) – 17%
Overall, 56% of participants showed a favourable response to therapy.
Despite these promising results, many other participants did not have changes in the nature of their anal lesions. However, even in participants whose lesions did not change, 5-FU may have had some benefit, because in 16 participants the anal lesions were stable in nature; that is, they did not become more abnormal. One participant’s lesions grew worse, transforming from an abnormal to highly abnormal state.
No participant developed invasive anal cancer during the study.
The study team attempted to monitor participants who responded to 5-FU over the long-term, but only 24 men returned to the clinic six months after their treatment with 5-FU ended. High-resolution anoscopy revealed that abnormal cells were once again detected in 50% of these men who initially had their anal lesions completely resolve. In two of these 24 men, the lesions had become precancerous. Doctors used electrical current to destroy the lesions.
Before the use of 5-FU, 43 patients had detectable HPV genetic material (DNA), and 95% of these men had high-risk types of HPV that are associated with anal cancer. On average, regardless of whether or not anal lesions resolved, 5-FU treatment had the following effect:
- It significantly decreased the types (or strains) of HPV that could be detected.
Overall, 85% of participants reported side effects from exposure to 5-FU, distributed as follows:
- 37% – mild side effects
- 48% – moderate side effects
No severe side effects, such as anal bleeding or tears to the anus, occurred in this study. Furthermore, while side effects were common, only two participants left the study because of them.
Readers should bear in mind that this was a pilot study, and because there was no comparison group simultaneously enrolled and because of other issues related to the design of this study its results are not definitive. 5-FU seemed to be associated with side effects that were tolerated by the majority of participants. The best dose and schedule of 5-FU for treatment of intra-anal lesions is not clear. Some doctors may not favour the use of 5-FU because of its potential for causing skin irritation and the relatively high recurrence rate of lesions. Despite these drawbacks, the German-Dutch team calls for a clinical trial comparing different treatments for abnormal anal growths in HIV-positive people.
—Sean R. Hosein
Richel O, Wieland U, de Vries HJ, et al. Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in HIV-positive men. British Journal of Dermatology. 2010; in press.