No Link Found Between Cancer and Bisphosphonate Use
Based on research by John Bilezikian, MD
There appears to be no relationship between the use of bisphosphonates and the development of cancer, according to researchers at Columbia University College of Physicians and Surgeons.
A letter to the editor in the January 1, 2009, issue of the New England Journal of Medicine cited reports of esophageal cancer following treatment with alendronate as well as alendronate combined with other oral bisphosphonates. Since then, controversy has surrounded this issue.
"We need to rectify this issue. There is no relationship between the use of bisphosphonates and esophageal cancer," said John Bilezikian, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York.
In a study presented at the 31st annual meeting of the American Society for Bone and Mineral Research, Bilezikian and his colleagues examined clinical and postmarketing data regarding risedronate. This agent has been studied in placebo-controlled phase 3 trials for up to 3 years and in more than 19,000 patients. Risedronate has also been studied in active-controlled studies with 4000 additional patients.
Patients in the placebo-controlled studies were randomized to receive risedronate 2.5 mg daily (N = 4998), risedronate 5 mg daily (N = 5395), or placebo daily (N = 5363). The incidence of esophageal cancer in these combined risedronate studies was 0.04% (two patients) in the 2.5-mg group, 0.02% (one patient) in the 5-mg group, and 0.04% (two patients) in the placebo group.
Overall, the researchers found that the incidence rate for esophageal cancer was 19 per 100,000 patient-years of observation in placebo patients, 22 per 100,000 in the 2.5-mg, daily patients, and 9 per 100,000 in the 5-mg-daily patients. In the active-control studies, no cases of esophageal cancer were reported in prevention, flexible-dosing, male osteoporosis, or open-label extension studies.
In postapproval surveillance from May 1998 to January 9, 2009, with more than 18 million patient-years of exposure, reported esophageal cancer coincident with risedronate use was very rare or less than 0.1 per 100,000 patientyears of exposure.
"Many clinicians and their patients are confused about this issue," said Bilezikian in an interview with The Oncology Pharmacist. "After the New England Journal report, patients started calling their physicians and saying 'I am not going to take that medicine,' but it wasn't true and they were misled. We are now trying to make the point by using data to argue that the report was not well founded."
He said healthcare providers should re assure their patients that there is no link between bisphosphonate use and esophageal cancer. According to the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) database, the incidence of esophageal cancer in American men and women 65 years of age is 23.3 per 100,000 per year. In Caucasian women 65 years of age, the incidence is 11.2 per 100,000 per year. Bilezikian said the incidence of esophageal cancer events observed among risedronate or placebotreated patients was consistent with the background rates in the population.
David Prelutsky, MD, associate clinical professor of medicine at Washington University School of Medicine, St. Louis, Missouri, said these finding are very important because they help clarify this area of controversy.
"This study is clinically relevant, as it reassures primary care physicians, who prescribe the bulk of bisphosphonates, that they are doing no harm. No physician wants to prevent one problem and then possibly cause another with a treatment. These data are reassuring," said Prelutsky in an interview with The Oncology Pharmacist.
