Wednesday, September 22, 2010
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September 9, 2010 — In an about face of findings, a new study reports that oral bisphosphonates — widely prescribed for osteoporosis — are associated with an increased risk for esophageal cancer. The study comes just weeks after another study, using the same database, found no such link.
The new case–control study found that the risk was statistically significant among patients who had 10 or more prescriptions for the drugs — compared with patients who had 1 to 9 prescriptions.
The relative risk also increases with duration of use; it doubles over about a 5-year period, according to the authors of the new study, led by Jane Green, PhD, a clinical epidemiologist from the Cancer Epidemiology Unit at the University of Oxford in the United Kingdom.
However, an expert in gastroesophageal cancer contacted by Medscape Medical News suggested that clinicians should not stop prescribing oral bisphosphonates.
Clinicians need to weigh the benefits of oral bisphosphonates such as the reduction in hip fracture against the risks such as the increase in esophageal cancer, said Gerard Blobe, MD, associate professor of medicine at Duke University School of Medicine in Durham, North Carolina.
"The absolute risk increase found in the study is still pretty small — 1 in 1000 to 2 in 1000 with about 5 years of use of oral bisphosphonates," he observed about the new data.
"I would say that, generally, the benefits outweigh the risks," he said.
Dr. Blobe also explained that oral bisphosphonates could theoretically cause esophageal cancer because "irritation" of the esophagus might "set the stage for cancer in some patients."
The new study's findings on oral bisphosphonates conflict with a recent British study that found no link.
Notably, both studies used the UK General Practice Research Database.
"What would cause these differences [in findings]?" asks an editorial that accompanies the new study, both of which were published online September 2 in BMJ.
A "major difference" in the 2 studies is the average length of follow-up, notes the editorialist, Diane Wysowski, PhD, an epidemiologist at the US Food and Drug Administration (FDA) in Silver Spring, Maryland. The earlier negative study had 4.5 years of follow-up; the new positive study has 7.5 years.
The positive study also had "an adequate sample size," said Dr. Wysowski.
Dr. Green and her coauthors said that their positive study had "greater statistical power" than the negative study — with 5 matched controls per case, compared with equal numbers in the exposed and comparison groups in negative study.
Even if oral bisphosphonates cause cancer, "the incidence of esophageal cancer in this population of users would be expected to remain relatively low," writes Dr. Wysowski.
Despite this comment, another gastroenterologist from Duke said that esophageal cancer is of growing concern in the United States and other industrialized countries.
"The incidence of esophageal adenocarcinoma is rising more rapidly than any other malignancy in the past 5 years in Western countries. The reasons are unknown," said Ivy Altomare, MD, assistant professor of medicine and a colleague of Dr. Blobe.
Advice to Patients
The immediate question for clinicians is what to tell patients, says Dr. Wysowski. Her primary recommendation is to tell patients to take the pills correctly. Dr. Blobe explained the reason for the recommendation.
As soon as it was recognized that oral bisphosphonates were associated with esophageal problems, the package inserts for these drugs were changed, he said. The change included directions on how to best take the drugs, and dictated that patients with a history of esophageal problems not be prescribed these agents.
After the package insert was changed, "the incidence of esophageal-related problems with the drugs subsequently dropped," he said. This chain of events suggests that noncompliant patients might be the ones who develop problems, he said.
Dr. Wysowski reminds clinicians to reinforce directions for drug usage with each prescription. Namely, remind patients to take oral bisphosphonates in the morning with a full glass of plain water on an empty stomach — at least 30 to 60 minutes before the first food, beverage, or medication.
Also tell patients not to recline for at least 30 to 60 minutes after taking an oral bisphosphonate.
The new study results might be, in an odd way, useful to clinicians, suggested Dr. Blobe. "This result could incentivize patients to take the pill correctly," he said.
The new case–control study found that the risk was statistically significant among patients who had 10 or more prescriptions for the drugs — compared with patients who had 1 to 9 prescriptions.
The relative risk also increases with duration of use; it doubles over about a 5-year period, according to the authors of the new study, led by Jane Green, PhD, a clinical epidemiologist from the Cancer Epidemiology Unit at the University of Oxford in the United Kingdom.
However, an expert in gastroesophageal cancer contacted by Medscape Medical News suggested that clinicians should not stop prescribing oral bisphosphonates.
Clinicians need to weigh the benefits of oral bisphosphonates such as the reduction in hip fracture against the risks such as the increase in esophageal cancer, said Gerard Blobe, MD, associate professor of medicine at Duke University School of Medicine in Durham, North Carolina.
"The absolute risk increase found in the study is still pretty small — 1 in 1000 to 2 in 1000 with about 5 years of use of oral bisphosphonates," he observed about the new data.
"I would say that, generally, the benefits outweigh the risks," he said.
Dr. Blobe also explained that oral bisphosphonates could theoretically cause esophageal cancer because "irritation" of the esophagus might "set the stage for cancer in some patients."
The new study's findings on oral bisphosphonates conflict with a recent British study that found no link.
Notably, both studies used the UK General Practice Research Database.
"What would cause these differences [in findings]?" asks an editorial that accompanies the new study, both of which were published online September 2 in BMJ.
A "major difference" in the 2 studies is the average length of follow-up, notes the editorialist, Diane Wysowski, PhD, an epidemiologist at the US Food and Drug Administration (FDA) in Silver Spring, Maryland. The earlier negative study had 4.5 years of follow-up; the new positive study has 7.5 years.
The positive study also had "an adequate sample size," said Dr. Wysowski.
Dr. Green and her coauthors said that their positive study had "greater statistical power" than the negative study — with 5 matched controls per case, compared with equal numbers in the exposed and comparison groups in negative study.
Even if oral bisphosphonates cause cancer, "the incidence of esophageal cancer in this population of users would be expected to remain relatively low," writes Dr. Wysowski.
Despite this comment, another gastroenterologist from Duke said that esophageal cancer is of growing concern in the United States and other industrialized countries.
"The incidence of esophageal adenocarcinoma is rising more rapidly than any other malignancy in the past 5 years in Western countries. The reasons are unknown," said Ivy Altomare, MD, assistant professor of medicine and a colleague of Dr. Blobe.
Advice to Patients
The immediate question for clinicians is what to tell patients, says Dr. Wysowski. Her primary recommendation is to tell patients to take the pills correctly. Dr. Blobe explained the reason for the recommendation.
As soon as it was recognized that oral bisphosphonates were associated with esophageal problems, the package inserts for these drugs were changed, he said. The change included directions on how to best take the drugs, and dictated that patients with a history of esophageal problems not be prescribed these agents.
After the package insert was changed, "the incidence of esophageal-related problems with the drugs subsequently dropped," he said. This chain of events suggests that noncompliant patients might be the ones who develop problems, he said.
Dr. Wysowski reminds clinicians to reinforce directions for drug usage with each prescription. Namely, remind patients to take oral bisphosphonates in the morning with a full glass of plain water on an empty stomach — at least 30 to 60 minutes before the first food, beverage, or medication.
Also tell patients not to recline for at least 30 to 60 minutes after taking an oral bisphosphonate.
The new study results might be, in an odd way, useful to clinicians, suggested Dr. Blobe. "This result could incentivize patients to take the pill correctly," he said.
# posted by roodbont @ 1:48 AM 
