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.