DFMO Shows Potential in the Prevention of Cervical Cancer

NEW ORLEANS--In a phase I trial from M.D. Anderson Cancer Center,the chemopreventive agent difluorometh-ylornithine (DFMO) producedsignificant regression of cervical intraepithelial neoplasia (CIN)grade 3, Michele Follen Mitchell, MD, reported at the Societyof Gynecologic Oncologists meeting.

DFMO is a suicide inhibitor of ornithine decarboxylase, a stepalong the polyamine synthesis chain to carcinogenesis, and isbelieved to be a strong antiprolif-erative agent. It has beenused in the treatment of colon cancer.

The study included 30 patients treated for 30 days with one offour doses of DFMO in elixir form: 1.0, 0.5, 0.25, and 0.06 g/m²/day.

After treatment, the patients underwent biopsies for polyaminesynthesis markers followed by loop electrosurgical excision ofthe cervix for complete his-topathologic study. Blood was drawnfor red cell polyamine synthesis markers and serum ornithine andarginine levels. One patient was excluded from analysis, leaving29 for evaluation.

Despite the short duration of treatment, five patients experienceda complete response, and 10 patients had a 50% response, showingregression of the lesion from CIN 3 to CIN 1 or 2. The DNA indexconfirmed the significance of the changes from pretreatment topost-treatment biopsies, Dr. Mitchell said.

While the classic polyamine markers were modulated, these changeswere not significant, probably because of the small sample size,Dr. Mitchell said.

Tissue polyamine modulation, as measured by the spermidine/spermineratio, on the other hand, was significantly changed at a DFMOdose of 1.0 g. Serum polyamine modulation, as measured by plasmaarginine, was also significantly modulated at the 1.0 g dose.This suggests that parts of the polysynthesis chain were blocked,possibly impeding car-cinogenesis, she said.

The provides optimism for the potential use of DFMO in the preventionof cervical cancer and will be further examined in a phase IIstudy, she said.