An analysis of adverse events reported to the U.S. Food & Drug Administration (FDA) indicates that the risk of esophageal cancer from oral bisphosphonates may be much higher than thought. The analysis, which was presented last month at the annual conference of the American Society of Clinical Oncology, also found that Fosamax (alendronate) was associated with the greatest number of esophageal cancer reports.
Fosamax, the first bisphosphonate to come to market in 1995, is approved to treat post-menopausal osteoporosis and Paget’s disease of bone. Other oral bisphosphonates include Actonel (risedronate), Boniva (ibandronate), Atelvia (risedronate delayed release), Didronel (etidronate), and Skelid (tiludronate). According to the FDA, oral bisphosphonates can cause irritation of the esophagus, leading to esophagitis or esophageal ulcers, which may bleed. Both of these conditions are known to be risk factors for esophageal cancer.
The FDA has been investigating a possible link between the use of Fosamax and other oral bisphosphonates and esophageal cancer. Last June, in Drug Safety Communication issued to update the public on the status of its review, the agency noted that the two studies it reviewed had reached conflicting conclusions. One study found no increase in the risk of esophageal cancer. The second study found a doubling of the risk of esophageal cancer among patients who had 10 or more prescriptions of the drugs, or who had taken the drugs over 3 years. Both studies drew data from the U.K.’s General Practice Research Database.
An analysis of the FDA database in 2009 found only 23 reports of esophageal cancer associated with Fosamax, but none associated with other oral bisphosphonates. However, Actonel, Boniva, and Didronel had been named in 31 reports in Europe and Japan.
For this new study, a group of researchers from Northwestern University in Chicago searched the FDA adverse event database for terms related to esophageal cancer in combination with all drug names for bisphosphonates over the period from 1996 to 2010. Overall, 128 cases of bisphosphonate-associated esophageal cancer were reported to the FDA in that time period. Fosamax accounted for 75% of the cancers found in the database search. In total, 96 cases of esophageal cancer were reported in relation to Fosamax, 14 with Actonel, and 10 with Boniva. Injectable bisphosphonates were also named in cancer reports, seven with Zometa/Reclast, and one with Aredia. Three of the cancer cases turned up by the search also noted Barrett’s esophagus, a known risk factor for cancer.
“Our analysis of FDA AERS identifies a larger number of cases of esophageal cancer than previously described, and a significant safety signal with alendronate use,” the study authors wrote. “Increased awareness and vigilance is needed for patients receiving oral bisphosphonate therapy.”
The researchers advised that use of oral bisphosphonates be avoided in patients with Barrett’s esophagus and persistent mucosal abnormalities.