Esophageal Cancer in Patients Taking Oral Bisphosphonates

Zosia Chustecka

December 31, 2008

December 31, 2008 — Cases of esophageal cancer in patients who had been taking oral bisphosphonate drugs for osteoporosis have been reported by an official from the Food and Drug Administration (FDA) in the January 1 issue of the New England Journal of Medicine.

Twenty-three cases (of which 8 were fatal) have been reported in the United States, all of them in association with alendronate (Fosamax, Merck), which was cited as the suspect drug in 21 cases and as a concomitant drug in 2 cases. These reports were received by the FDA in the 12-year period between October 1995 (when alendronate was launched in the United States) and mid-May 2008. No reports were received about esophageal cancer and any of the other oral bisphosphonate products.

A further 31 cases (6 fatal) have reported in Europe and Japan, with alendronate as the suspected drug in 21 cases. Of the remainder, 6 cases were associated with risedronate (Actonel, Procter & Gamble/Sanofi-Aventis), ibandronate (Boniva, Roche/GlaxoSmithKline), etidronate (Didronel, Procter & Gamble), or a combination of these, and 4 cases cited bisphosphonates as concomitant drugs.

Writing in a letter to the journal, Diane Wysowski, PhD, from the FDA, gives few further details but points out that 4 of the patients had Barrett's esophagus, which is a precursor of esophageal adenocarcinoma. "Physicians should avoid prescribing oral bisphosphonates to patients with Barrett's esophagus," she writes.

Dr. Wysowski also points out that esophagitis has been associated with oral bisphosphonates, usually when the drugs are not taken according to directions. "Crystalline material similar to ground alendronate tablets has been found in patients with erosive esophagitis, and persistent mucosal abnormalities have been noted in some of these patients, suggesting a potential for carcinogenic effects," she writes.

Merck said in a statement that data from its clinical trials and postmarketing reports do not suggest any association between alendronate and esophageal cancer. The company pointed out that alendronate has been marketed for 13 years, during which time more than 150 million prescriptions have been written in the United States alone. Merck also noted that its clinical database includes more than 17,000 patients, of whom about 3000 osteoporosis patients took alendronate for 3 to 5 years and about 800 patients took alendronate for 8 to 10 years.

N Engl J Med. 2009;1360:89-90.

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