The antiarrhythmic drug amiodarone is associated with an increased risk of cancer, but the effect is significant only in men or at higher doses, according to a Taiwanese population-based cohort study published online April 8 in Cancer.
"We found that there was a borderline significantly increased risk of cancer among patients who received amiodarone compared with the general population," wrote Dr. Vincent Yi-Fong Su of the Taipei (Taiwan) Veterans General Hospital and his colleagues. Patients either of male sex or with more than 180 cumulative defined daily doses within the first year "had a significantly higher risk of developing cancer, and those with both factors had an even greater SIR [standardized incidence ratio] of 1.46 (P = .008)."
Amiodarone can build up in the soft tissues and increase the risk of lung masses, thyroid cancer, and skin cancer.
While all patients receiving amiodarone had a slight increase in their overall risk of cancer (SIR, 1.12; 95% CI, 0.99-1.26; P = .067), the risk was significantly higher in men (SIR, 1.18; 95% CI, 1.02-1.36; P = .022) but not in women (SIR, 0.99; 95% CI, 0.79-1.23).
"One possible explanation for this difference is that there is a 37% higher clearance rate of amiodarone in females than in males because of differences in cytochrome P450 3A4 activity and the percentage of body fat," the authors reported.
The study also found a dose-dependent relationship between amiodarone and cancer risk. Among patients in the middle and top tertile of cumulative defined daily dose, the adjusted hazard ratios were 1.70 (95% CI, 1.02-2.84; P = .042) and 1.98 (95% CI, 1.22-3.22; P = .006) respectively, after adjustment for age, sex, and comorbidities.
The researchers examined data from 6,418 patients treated with amiodarone, 43% of whom were female, using information from the Taiwan National Health Insurance Research Database.
During the median 2.6-year follow-up, 280 patients developed cancer, with no significant differences found in the type or location of cancer. Amiodarone, approved by the Food and Drug Administration in 1985, is a fat-soluble drug with a long elimination half-life, so large amounts of the drug can build up in the soft tissues after prolonged treatment, and postmarketing surveillance had suggested an increased risk of lung masses, thyroid cancer, and skin cancer.
The researchers noted an increase in the incidence of cancer in the first year after amiodarone therapy (SIR, 1.32; 95% CI, 1.05-1.64; P = .002), although they suggested this may be due to surveillance bias (Cancer 2013 April 8 2013 [doi.wiley.com/10.1002/cncr.27881].
"To provide an initial, thorough evaluation of the etiology of arrhythmias and to monitor the toxicity of amiodarone in follow-up studies, an increased number of medical examinations are performed in patients treated with amiodarone," the authors wrote. "Thus, the cancer incidence within the first year falsely increases due to early detection."
While the study excluded patients with preexisting malignancies, researchers were not able to account for other risk factors, such as obesity, smoking and alcohol use, environmental exposure, and family history of cancer.
The authors concluded that while extensive screening for occult cancers in patients taking amiodarone was not practical, they advocated closer surveillance of cancer events in future amiodarone trials.
The study was partly supported by the Taipei (Taiwan) Veterans General Hospital. The authors reported no relevant financial conflicts.