A NOVEL INDICATION FOR CETUXIMAB

NEW YORK (Reuters Health) Nov 25 - Treatment with cetuximab (Erbitux) significantly improves the signs and symptoms of Menetrier's disease, sometimes leading to near-resolution, the findings of a small study show.

"Because no other medical therapies have shown to be consistently beneficial, cetuximab should be considered as first-line therapy for Menetrier's disease," senior author Dr. Robert J. Coffey and colleagues at the Vanderbilt University School of Medicine in Nashville conclude.

Also known as hypoproteinemic hypertrophic gastropathy, Menetrier's disease is a rare premalignant hyperproliferative disorder of the stomach with no known cure other than gastrectomy.

The disease is characterized by enlarged gastric folds, decreased acid production, excess mucus secretion, and hypoalbuminemia. Symptoms may include abdominal pain, nausea and vomiting, peripheral edema, and chronic gastric blood loss.

Evidence from both mice and humans indicates that the histologic abnormalities are associated with increases in transforming growth factor (TGF)-alpha. Cetuximab, a monoclonal antibody that binds to the epidermal growth factor receptor, inhibits binding of TGF-alpha.

In the November 25th issue of Science Translational Medicine, the researchers report that their treatment of one patient with cetuximab led to marked clinical and biochemical improvement.

Based on that success, they administered a one-month course of treatment to nine patients (ages 29 to 79) with severe Menetrier's disease, all of whom were considering gastrectomy. (The disease is so rare, notes an editorial commentary, that it took the researchers eight years to assemble these nine patients.)

Patients were treated with a loading dose of IV cetuximab (400 mg/m2 of body surface area), followed by three weekly IV infusions of 250 mg/m2. One patient withdrew after the first dose due to concerns over potential side effects. A second patient withdrew after two infusions when persistent abdominal pain led to the diagnosis of gastric cancer.

The seven patients who completed the study showed significant improvement within days of starting treatment. By the end of the month, the primary outcomes - scores on the overall Quality of Life Index and the Health and Functioning subscale - were significantly improved. Furthermore, parietal cell mass had increased, mean gastric pH had fallen from 6.0 to 4.0, and there was a trend toward decreased stomach wall thickness (from 13.7 to 9.6 mm).

All seven patients chose to continue treatment (follow-up 8 to 40 months). Four had near-complete histologic resolution of their illness. Four patients elected to undergo gastrectomy despite improvement (including one with near-complete resolution), primarily over fears of gastric cancer and concerns about indefinite treatment with cetuximab. One patient had a dysplastic lesion more than a year after discontinuing treatment.

While treatment with cetuximab may help patients avoid gastrectomy altogether, the authors note that the drug might also be used as a "bridge" to improve the operative risk of poor surgical candidates.

Sci Transl Med 2009.