Reports of Esophageal Cancer with Oral Bisphosphonate Use

Abstract

Between the time of the initial marketing of alendronate in October 1995 through mid-May 2008, the Food and Drug Administration (FDA) received reports of 23 patients in the United States receiving a diagnosis of esophageal cancer, with alendronate (Fosamax, Merck) as the suspect drug (in 21 patients) or the concomitant drug (in 2 patients). No similar U.S. reports for other oral bisphosphonates were retrieved from the FDA's database for adverse-event reporting. Eight deaths were reported. Of the 23 patients, 18 (78%) were women; the median age was 74.0 years (mean, 71.8; based on 19 patients). Among the 14 patients with dose information, 8 were reported to have taken alendronate at a dose of 10 mg per day; 5 were reported to have taken 70 mg per week; and 1 was reported to have taken alendronate “once per week.” The median time from alendronate use to diagnosis was 2.1 years (range, 0.5 to 10.0; mean, 3.0; based on 16 patients). Information about risk factors was not provided for all patients, but one patient took alendronate despite having Barrett's esophagus, a precursor of esophageal adenocarcinoma. The predominant site mentioned was the distal esophagus (in six patients), with gastric involvement in some cases. Histologic analysis showed adenocarcinoma in seven patients and squamous-cell carcinoma in one patient.