FYI: APDA Asks – Is there a connection between Melanoma, Levodopa and PD?

 

The following article was written by Diane Church and appeared in the APDA online newsletter recently

LEVODOPA, MELONOMA, AND PARKINSON’S DISEASE: IS THERE A CONNECTION?

by Diane L. Church, PhD

New Hampshire APDA Information & Referral Center Coordinator 

Levodopa was approved as a treatment for Parkinson’s disease in 1968 by the US Food and Drug Administration. In the form of carbidopa-levodopa (Sinemet®), it remains the most common treatment for Parkinson’s nearly 45 years later.

In 1972, the case of a PD patient who was treated with levodopa and suffered recurrent malignant melanoma skin cancer was reported. Other cases were subsequently published, and by 1976 it was announced that use of levodopa in Parkinson’s patients with melanoma was contraindicated.(3)  However, studies had not answered the question: Was the occurrence of melanoma in Parkinson’s patients actually caused by levodopa, or was it a coincidence?

At the time, it seemed plausible that there could be an association between levodopa treatment and melanoma incidence: Levodopa is the substrate for the synthesis of both dopamine and melanin, which is the substance that accumulates in the darkly pigmented cells of melanoma.(2,3,6).  Numerous studies (1-6) have now shown that people with Parkinson’s are at higher risk for melanoma, but that the increased incidence of melanoma is not related to any PD medication. Instead, it appears that “melanoma and PD might have shared environmental or genetic risk factors or pathogenic pathways.”(4)

Surprisingly, the Physician’s Desk Reference (PDR) still states that carbidopa-levodopa is contraindicated for those with undiagnosed skin lesions or a history of melanoma! It is no wonder that many in the Parkinson’s community, as well as numerous medical personnel who do not specialize in PD, still believe that there is a causal link between levodopa and melanoma. Unfortunately, many who would have received relief of their PD symptoms by taking levodopa have avoided this medication for fear of getting melanoma.

More on Melanoma from the National Institutes of Health (NIH):

“A mole, sore, lump, or growth on the skin can be a sign of melanoma or other skin cancer. A sore or growth that bleeds, or changes in skin coloring may also be a sign of skin cancer.

The ABCDE system can help you remember possible symptoms of melanoma:

Asymmetry: One half of the abnormal area is different from the other half.
Borders: The edges of the growth are irregular.
Color: Changes from one area to another, with shades of tan, brown, or black, and sometimes white, red, or blue or a mix of colors within one sore.
Diameter: The spot is usually (but not always) larger than 6 mm in diameter — about the size of a pencil eraser.
Evolution: The mole keeps changing appearance.

The key to successfully treating melanoma is recognizing symptoms early. You might not notice a small spot if you don’t look carefully. Have yearly body checks by a dermatologist, and examine your skin once a month. Use a hand mirror to check hard-to-see places. Call your doctor if you notice anything unusual.”

The NIH also states that the risk of developing melanoma increases with age, and that you are more likely to develop melanoma if you:

-  Have fair skin, blue or green eyes, or red or blond hair
-  Live in sunny climates or at high altitudes
-  Spent a lot of time in high levels of strong sunlight or use tanning devices
-  Have close relatives with a history of melanoma

Some Take-Home Messages

1)  Levodopa treatment is NOT associated with an increase in diagnosis of melanoma or other cancers.
2)  People with Parkinson’s:
-    have an estimated 2- to 6-fold increased risk of melanoma
-    have a reduced risk of most other types of cancer
3)  Melanoma is rare in the general population (based on 2007-2009 data, only 2% of those born today will be diagnosed with melanoma in their lifetimes.(8)
4)  The estimated lifetime melanoma rate for those with PD is therefore 4-12%.
5)  Malignant melanoma is a curable disease if treated early. If left untreated, it is potentially fatal.

References:
1. Bertoni JM, Arlette JP, Fernandez HH, et al. Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. Arch Neurol 2010; 67:347-352
2. Driver JA, Logroscino G, Buring JE, et al. A prospective cohort study of cancer incidence following the diagnosis of Parkinson’s disease. Cancer Epidemiol Biomarkers Prev 2007; 16: 1260-1265
3. Ferreira JJ, Neutel D, MestreT et al. Skin Cancer and Parkinson’s Disease (Review). Movement Disorders 2010; 25: 129-148.
4. Liu R, Gao, X, Lu Y, Chen, H. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 2011; 76: 2002-2009
5. Weiner WJ, Singer C, Sanchez-Ramos JR, Goldenberg JN. Levodopa, melanoma, and Parkinson’s disease. Neurology 1993; 43: 674-677
6. Zannetti R, Rosso S, Loria DI. Parkinson’s Disease and Cancer (Commentary) Cancer Epidemiol Biomarkers Prev 2007; 16: 1081
7. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001853/ (accessed August 8, 2012)
8. http://seer.cancer.gov/statfacts/html/melan.html (accessed August 8, 2012)

Reprinted with permission from the Parkinson’s Companion (A publication of the APDA Information & Referral Center at Dartmouth-Hitchcock Medical Center, Lebanon, NH), Fall 2012.