Research ArticleMénétrier’s Disease

Efficacy of Cetuximab in the Treatment of Ménétrier’s Disease

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Science Translational Medicine  25 Nov 2009:
Vol. 1, Issue 8, pp. 8ra18
DOI: 10.1126/scitranslmed.3000320

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Smoothing the Ménétrier’s Stomach

The inner surface of the stomach might be viewed as uneven terrain—it’s covered with millions of pits that contain gastric glands and is folded into a series of ridges called rugae. This topography seems mild, however, in comparison to what’s seen in Ménétrier’s disease, a rare, chronic disorder in adults. In this condition, because of overgrowth of the mucous cells that line the inside of the stomach, the rugal folds become so massively enlarged that the stomach interior almost resembles the convoluted surface of the brain, as first noted by Pierre Ménétrier in 1888. The gland cells, in contrast, are reduced in number. These changes result in production of too much mucus and too little stomach acid, along with protein loss across the stomach lining, which leads to the accumulation of fluid in the feet and ankles and malnutrition. Patients suffer from severe vomiting and abdominal pain and have an increased risk of stomach cancer. With no effective drugs for treating this disease, the last line of defense has been removal of part or all of the stomach. Now, Coffey and colleagues describe nearly complete remission of this disease in several patients after a clinical trial testing a new therapy.

Ménétrier’s disease symptoms appear to result from excess stimulation of the epidermal growth factor receptor (EGFR) by one of its ligands, transforming growth factor–α, which is overproduced in the stomach of patients with this condition. This too-active EGFR has been linked to several cancers, including lung, brain, and colon cancer, and as a result, a number of EGFR inhibitors have been developed as cancer therapeutics. Cetuximab, a monoclonal antibody that binds to the extracellular region of EGFR and blocks signaling, is used to treat colorectal and head and neck cancer. Because of the link between EGFR and Ménétrier’s disease, and the lack of any effective drugs for this disease, a number of years ago Coffey’s group received approval to treat an individual with Ménétrier’s disease with cetuximab. This treatment led to substantial improvement in the patient’s symptoms and biochemical indicators of the disease.

On the strength of that result, Coffey’s group then undertook a trial of cetuximab in nine other patients with Ménétrier’s disease. Because the disease is so rare, it took 8 years to gather these patients. Seven patients completed the 1-month trial, during which cetuximab was delivered intravenously once a week, and all showed marked improvement in clinical, biochemical, and histological features of the disease. All seven patients chose to continue treatment and four of them later showed almost complete remission, indicating that cetuximab is an effective treatment for Ménétrier’s disease.

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