The Food and Drug Administration (FDA) has concluded that the use of entacapone to treat Parkinson disease (PD) does not increase the risk of developing prostate cancer.
Previously in March 2010, the FDA notified healthcare professionals and patients that the use of entacapone may be associated with an increased risk of prostate cancer based on the STRIDE-PD (Stalevo Reduction in Dyskinesia Evaluation – Parkinson Disease) clinical trial. As a result, Novartis, the manufacturer of Comtan (entacapone) and Stalevo (entacapone/carbidopa/levodopa), was required by the FDA to conduct a study to further investigate this potential risk.
The study compared the incidence rate of prostate cancer in a cohort of patients treated with entacapone plus a conventional PD treatment of dopa decarboxylase inhibitor/levodopa (DDCI/LD) with a cohort of patients treated with DDCI/LD plus either a dopamine agonist or a monoamine oxidase B inhibitor. Of the total 11,396 PD patients in the study, 1141 received entacapone.
Results showed that over an average follow-up of 4.6 years, 359 prostate cancer cases were reported. Treatment with DDCI/LD with add-on entacapone was not associated with an increased risk of prostate cancer (hazard ratio [HR] 1.05; 95% CI, 0.76-1.44) or prostate cancer death (HR 0.93; 95% CI, 0.43-1.98) compared with treatment without add-on entacapone. In addition, study findings did not demonstrate a link between longer cumulative treatment with entacapone and increased prostate cancer or prostate cancer mortality risk (secondary end points); HR estimates for >360 days cumulative treatment with entacapone were 0.82 (95% CI, 0.56-1.18) for prostate cancer incidence and 1.27 (95% CI, 0.59-2.72) for prostate cancer death, respectively, compared with no entacapone treatment.
The FDA also conducted an independent retrospective cohort study using data from the Department of Veteran Affairs healthcare system. The study included 17,666 patients with PD treated with levodopa-carbidopa (n=5257) and compared add-on entacapone therapy to add-on therapy with a dopamine agonist or monoamine oxidase B inhibitor (control group; n=12,409).
Results showed that 23 prostate cancer cases occurred in the entacapone cohort and 97 in the control group over a mean follow-up time of 3.1 years and 4.0 years, respectively. Moreover, when evaluating risk based on increased duration of cumulative entacapone treatment of >2 years, no difference in prostate cancer risk was observed between the groups (adjusted HR 1.08; 95% CI, 0.46-2.51).
Patients and healthcare professionals are urged to report any adverse events related to entacapone-containing products to the FDA MedWatch program.
For more information visit fda.gov.