Amiodarone Linked to Increased Cancer Risk in Men

Roxanne Nelson

April 10, 2013

Amiodarone (Nexterone), an antiarrhythmic agent widely used to treat ventricular arrhythmias and atrial fibrillation, might be linked to an increased risk for cancer in men and those with prolonged exposure to the drug, according to study published online April 8 in Cancer.

All patients who received amiodarone had a borderline significant increase in overall risk for cancer, compared with the general population (standardized incidence ratio [SIR], 1.12; P =.067).

This risk was significantly higher in men (SIR, 1.18; P = .022), but not in women (SIR, 0.99). The risk also appeared to be dose dependent.

For all patients with a 1-year cumulative defined daily dose that exceeded 180, the SIR was 1.28 (P = .046). For men, the SIR was 1.46 (P = .008).

"We suggest that cancer events be routinely reported in future amiodarone trials, and further observational research is necessary," said researcher Vincent Yi-Fong Su, MD, from the Taipei Veterans General Hospital in Taiwan, in a statement. "Also, when prescribing amiodarone, doctors need to keep in mind that this medication may increase cancer risk."

US Food and Drug Administration postmarketing surveillance has reported cases of lung masses, thyroid cancer, and skin cancer associated with amiodarone, the researchers point out.

A meta-analysis of randomized trials unexpectedly found a borderline significant increase in cancer mortality in patients being treated with amiodarone, but there have not been any large-scale studies to date that have looked at this issue, they note.

Not Yet Practice Changing

"While we need to take note of these data, we should take them with a grain of salt," said James Marshall, PhD, senior vice president for cancer prevention and population sciences and chair of the Department of Cancer Prevention and Population Sciences at the Roswell Park Cancer Institute in Buffalo, New York.

There are a number of problems with the study, he told Medscape Medical News.

"There was only a 12% increase for the whole group, which is a small increase," Dr. Marshall said. "If this was a pristine study, it might mean something, but they are using standard incidence ratios, and those are notoriously difficult to interpret."

Standard incidence ratios compare the observed number of cases with the 'expected' number of cases in a population or geographic area, he explained.

Dr. Marshall also noted that although the researchers adjusted for age, sex, and comorbidities, they did not look at potential risk factors, such as smoking, environmental exposure, family history of malignancy, alcohol use, and obesity.

"We do want to make note of these results," he said, "but I don't think cardiologists are going to change treatment based on this 1 study alone. We need to be careful about coming to conclusions until we see some confirmation of this in other studies."

Study Details

In this population-based cohort study, Dr. Su and colleagues used the Taiwan National Health Insurance Research database to identify patients treated with amiodarone. The final cohort consisted of 6418 patients, and was observed from 1997 to 2008 (a total of 21,684 person-years). Median follow-up was 2.57 years.

During the study period, 280 cancers developed in the cohort. In a subgroup analysis on the basis of age, SIRs were not significantly different in the amiodarone group, except in men 20 to 59 years of age (SIR, 1.67; P = .025) and in men 80 years and older (SIR, 1.41; P = .016). The researchers note that the incidence of cancer rose in the first year of amiodarone therapy (SIR, 1.32; P = .002), but not after that (SIR, 1.02).

When cumulative defined daily dose was classified by tertile, for the tertile with the highest dose, the adjusted hazard ratio was 1.98 (P = .006); for the tertile with the intermediate dose, it was 1.70 (P = .042).

The researchers note that there was no significant difference in the incidence of cancer for each site between patients treated with amiodarone and the general population.

There were no significant differences in incidence for different types of cancer. For lung and mediastinum cancer, there were 44.00 observed cases and 39.41 expected cases (SIR, 1.12); for thyroid cancer, there was 1.00 observed case and 1.94 expected cases (SIR, 0.51); for skin cancer, there were 6.00 observed cases and 5.99 expected cases (SIR, 1.00).

The study was supported by Taipei Veterans General Hospital. The researchers have disclosed no relevant financial relationships.

Cancer. Published online April 8, 2013. Abstract

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