Does PD itself or treatments for it increase risk of developing malignant melanoma?
Patients with Parkinson’s disease have long been thought to have a 2-to 4-fold higher risk of developing malignant melanoma (skin cancer) than the general population. What scientists don’t know for certain is whether this increased risk is due to Parkinson’s disease itself or to specific treatments: levodopa (including levodopa/carbidopa, Sinemet, Sinemet-CR, levodopa/carbidopa plus Comtan, or Stalevo), one of the oldest, and Azilect, one of the newest.
Since the late 1970s, a warning has appeared in the prescribing literature for levodopa regarding the risk of activating malignant melanoma. Case reports suggested that levodopa has a causal relationship with this form of skin cancer due to their shared dopamine biochemical pathway. Evaluations of these reports, however, concluded that the occurrence of both Parkinson's disease and melanoma is “coincidental rather than causal.”(4) Patients on levodopa therapy did not appear to be predisposed to melanoma, nor did levodopa therapy appear to exacerbate melanoma if it were previously present.(4) In fact, levodopa has an “anti-tumor effect” on melanoma and can be used safely in PD patients with a history of melanoma.(5)
New Danish research findings appear to further “weaken the hypothesis that levodopa is causally related to an increased risk of malignant melanoma” in people with Parkinson’s disease.(2) Doctors from the Institute of Cancer Epidemiology in Copenhagen “examined the prevalence of malignant melanoma, skin carcinoma, and other cancers before a first hospitalization or outpatient visit for Parkinson's disease.”(2
The analysis compared the cancer histories of 8,090 patients with Parkinson's disease to those of 32,320 randomly selected controls. Participants eventually diagnosed with Parkinson's disease had a slightly higher prevalence of cancer at any site compared to controls. The incidence of malignant melanoma and skin carcinoma, however, was 44% and 26 % higher respectively in patients with Parkinson's disease compared with controls.(2)
Verdict still out on Azilect and skin cancer
A small number of patients taking Azilect during the drug’s development program were diagnosed with melanoma. The higher incidence of this form of skin cancer is comparable to the increased risk observed in people with Parkinson’s disease compared with rates in age- and sex- matched populations from two epidemiologic databases.(1)
The FDA has concluded that the available data do not link Azilect to an increased risk for melanoma. To definitively address this issue, the drug's manufacturer will perform a phase IV (post-market) study. In the interim, product labeling will recommend that patients undergo periodic dermatologic examinations to monitor for melanomas.(1)
(1) Miranda Hitti "FDA Approves Parkinson’s Disease Drug" WebMD Medical News Reviewed By Louise Chang, MD on May 18, 2006
(2) Reuter’s Health Information "Melanoma often seen before Parkinson's disease" Medline Plus September 26, 2006
(3) Siple JF, Schneider DC, Wanlass WA, Rosenblatt BK. "Levodopa therapy and the risk of malignant melanoma" Annals Pharmacotherapy (2000) 34: 382- 385
(4) Fiala KH, Whetteckey J, Manyam BV "Malignant melanoma and levodopa in Parkinson's disease: causality or coincidence?" Parkinsonism & Related Disorders (2003): 9: 321 - 327
(5) Weiner WJ, Singer C, Sanchez-Ramos JR, Goldenberg JN. "Levodopa, melanoma, and Parkinson's disease." Neurology (1993) 43: 674 - 677