NEW ORLEANS--In a phase I trial from M.D. Anderson Cancer Center, the chemopreventive agent difluorometh-ylornithine (DFMO) produced significant regression of cervical intraepithelial neoplasia (CIN) grade 3, Michele Follen Mitchell, MD, reported at the Society of Gynecologic Oncologists meeting.
DFMO is a suicide inhibitor of ornithine decarboxylase, a step along the polyamine synthesis chain to carcinogenesis, and is believed to be a strong antiprolif-erative agent. It has been used in the treatment of colon cancer.
The study included 30 patients treated for 30 days with one of four 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 polyamine synthesis markers followed by loop electrosurgical excision of the cervix for complete his-topathologic study. Blood was drawn for red cell polyamine synthesis markers and serum ornithine and arginine levels. One patient was excluded from analysis, leaving 29 for evaluation.
Despite the short duration of treatment, five patients experienced a complete response, and 10 patients had a 50% response, showing regression of the lesion from CIN 3 to CIN 1 or 2. The DNA index confirmed the significance of the changes from pretreatment to post-treatment biopsies, Dr. Mitchell said.
While the classic polyamine markers were modulated, these changes were not significant, probably because of the small sample size, Dr. Mitchell said.
Tissue polyamine modulation, as measured by the spermidine/spermine ratio, on the other hand, was significantly changed at a DFMO dose of 1.0 g. Serum polyamine modulation, as measured by plasma arginine, 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.