Shortly after levodopa's release, the author of this book, Dr. Abraham Lieberman, saw a person with PD who developed a recurrence of his melanoma after 4 months of treatment with levodopa. Melanoma is a pigmented cancer of the skin. If not recognized and treated, it can metastasize (spread) almost everywhere in the body, which can be fatal. However, even if a melanoma is recognized and removed, years later it can reappear. Melanoma contains an enzyme, tyrosine oxidase, that can use levodopa as an energy source: hence the question of a relationship of melanoma to levodopa. After Dr. Lieberman's report, other doctors reported people in whom there appeared to be a relationship between starting levodopa or Sinemet and recurrence of melanoma. However, there were equally as many people with a history of melanoma who were successfully treated with Sinemet in whom there was no recurrence of melanoma. A cause-and-effect relationship between Sinemet and the recurrence of a melanoma was claimed by some and denied by others. Despite the fact that Sinemet has never been observed to stimulate melanoma, more case reports followed and the anecdotal evidence that Sinemet accelerated the growth of melanoma increased. These reports resulted in the following warning in the Physicians' Desk Reference (a guide that doctors use in determining which drugs might be used for treating a condition) for Sinemet:
Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious, undiag-nosed skin lesions or a history of melanoma.
This warning first appeared in 1976 and continues to be reviewed.
In 1993, Dr. William Wiener undertook a review of the reported cases of possible association between Sinemet and melanoma. In addition he reported 9
people with PD who were treated with Sinemet despite a diagnosis of melanoma. Dr. Weiner made the following points:
If a person develops a recurrence of melanoma, the possibility must be raised that the melanoma is not a recurrence of the original melanoma but is a new primary melanoma (a melanoma unrelated to the original melanoma). It may be important, in terms of mechanisms, to distinguish, if possible, between a new melanoma that has not spread and a melanoma related to the first melanoma but one that has spread.
Multiple primary melanomas (two or more melanomas with each melanoma arising on its own without a relationship to the other melanoma) may occur in up to 4% of patients with melanoma, the second melanoma usually appearing within 5 years of the original melanoma. This risk of a secondary melanoma, unrelated to the first melanoma, makes it hard to assess the role, if any, of Sinemet in aggravating melanoma.
The natural history of melanoma is for late recurrence and irregular growth. It's estimated the incidence of melanoma (the number of new melanomas per year) is 9 new people with melanoma per 100,000 people. Given there are 1,000,000 people with PD, one would expect 90 new cases per year of melanoma in-patients with PD.
Dr. Wiener did not believe there is a relationship between levodopa, Sinemet, and melanoma. Two other doctors, Dr. Sober and Dr. Wick, prospectively examined 1,099 people in a study of people with melanoma and found only one person taking Sinemet. They concluded that the risk of developing melanoma could not be substantial and that there was little evidence to support a cause-and-effect relationship between melanoma and Sinemet.
At present, the evidence for a link between Sinemet and recurrence of melanoma is anecdotal and not well documented. Review of the previously reported cases that suggested such a link reveals other explanations. Several people with PD and melanoma have been successfully treated with Sinemet without a recurrence of their melanoma. With the current availability of dopamine agonists such as Mirapex and Requip— drugs not available when the initial link between Sinemet and melanoma was proposed—there are now alternatives to Sinemet in PD patients with melanoma. If the person then needs Sinemet, Sinemet should be started.
Was this article helpful?
Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.