cream had a 50% efficacy for the treatment of high-grade pre-cancerous anal and
vulvar lesions in HIV-positive people, US investigators report in the online
edition of AIDS. The small study
involved 33 patients who received up to six two-week courses of treatment.
Human papillomavirus (HPV)-associated cancers
of the anus and vulva are more common in HIV-positive people than the general
pre-cancerous lesions are the precursors to invasive anal and cervical cancer.
They are difficult to treat and have a high rate of recurrence.
Cidofovir is currently
licenced for the treatment of cytomegalovirus (CMV). It also has activity against
HPV. A number of small studies involving HIV-positive people have shown that
cidofovir is an effective therapy for genital warts and has a generally mild
side-effect profile. But little is known about
the safety and efficacy of cidofovir cream for the treatment of high-grade
pre-cancerous lesions of the anus and vulva in HIV-positive people.
therefore designed a prospective, open-label study involving 24 men and nine women
(eight who also had lesions of the vulva). The participants had biopsy-proven
high-grade lesions measuring at least 3 cm2.
The participants were
instructed to apply the study cream sparingly in a thin layer over the affected
area with a gloved finger once daily and to wash the cream off six to eight
hours later. Individuals received up to six two-week cycles of treatment.
Treatment response was evaluated after each treatment cycle.
- Complete response – absence of any high-grade
- Partial response – no new lesions and a 50% or
greater decrease in lesion area.
- Disease progression – a 25% or greater increase
in lesion size or the development of anal or cervical cancer.
The participants were
enrolled between February 2008 and August 2009. Their median age was 44 and 97%
were taking antiretroviral therapy. The median CD4 cell count was 412 cells/mm3
and median viral load was below 75 copies/ml. Average lesion size on enrolment
was 6.6 cm2.
A total of 26 people completed the study. Four were lost to follow-up, two withdrew because
of mild side-effects, and one person was excluded as biopsy results showed
that he did not have high-grade lesions.
In the intention-to-treat
analysis (comprising those who had completed the study as per protocol), 15% had a complete response and
36% had a partial response. Disease remained stable in 21% of individuals and
6% experienced disease progression with one participant developing anal cancer.
“The diagnosis of
cancer in one of our participants is concerning, and may represent an occult
lesion that was present prior to treatment and not sampled by biopsy,” comment
the investigators. “It could also be the failure of the study agent to prevent
progression of the precancerous lesion.”
All but one participant
(97%) reported side-effects. These were generally mild and consisted or
irritation, burning or ulceration at the site of treatment.
The authors were
encouraged by their results and conclude: “Phase 3 trials should be conducted
with more prolonged treatment courses and longer follow-up to assess the
durability of response.”