DFMO may offer chemopreventive effect in Barrett’s esophagus and dysplasia

AACR Frontiers in Cancer Prevention Research

Difluoromethylornithine may help to modulate biomarkers of cell proliferation in patients with Barrett’s esophagus and mucosal dysplasia, according to results of a pilot study.

The study results, presented by Frank Sinicrope, MD, professor of medicine and oncology at the Mayo Clinic in Rochester, Minn., demonstrated that treatment with DFMO was associated with suppressed mucosal putrescine levels. Furthermore, Kruppel-like factor 5 (KLF5) gene, a mediator of cell proliferation, was demonstrated to be downregulated with DFMO treatment.

Sinicrope said KLF5 may be a potential target for DFMO; this indicates the potential mechanism contributing to the chemopreventive effects of DFMO.

Sinicrope and his colleagues examined 10 patients with histologically confirmed Barrett’s esophagus and low-grade dysplasia. Patients were assigned DFMO at a dose of 0.5 g/m² per day given continuously for six months. An esophagoscopy with biopsies was performed for each patient at baseline, three months, six months and, where available, 12 months.

After six months of treatment with DFMO, one patient showed regression of dysplasia, one patient showed progression of dysplasia and eight patients showed stable disease. Among patients in the stable disease category, two patients with extensive low-grade dysplasia showed only focal dysplasia based upon four or more biopsies at six months. The researchers said histolopathological improvements seen at six months were maintained at 12 months.

According to Sinicrope, DFMO was well-tolerated. One patient reported hearing loss and balance-related problems that were related to DFMO treatment. – by Jay Lewis

For more information:
Sinicrope FA. #A61. Presented at: AACR Seventh Annual International Conference on Frontiers in Cancer Prevention Research; Nov. 16-18, 2008; Washington.