PD and Cancer Risk
On March 31, 2010, the FDA announced it was investigating the Parkinson's disease drug Stalevo for a possible association with prostate cancer. The announcement followed findings from a large trial, STRIDE-PD, which found an increased risk of prostate cancer in patients taking Stalevo.
The Michael J. Fox Foundation spoke with Susan Bressman, MD, about the implications of this announcement for patients as well as other research on cancer links to PD.
MJFF: What is Stalevo and why would it be prescribed to a patient?
SB: Stalevo is entacapone (COMTan) in combination with levadopa-carbidopa (Sinemet). Stalevo was approved for and is still used in patients who are fluctuating in the effect of Sinemet. Although these patients respond to the Sinemet treatment, they aren't getting a nice smooth response. Instead, some patients find that the Sinemet is wearing off, they know when their next dose is due and they are getting a shorter duration of benefit from each dose. For these patients, adding COMTan to Sinemet or switching to Stalevo can be helpful in keeping a more stable blood level and smoother effect in the brain.
MJFF: Why is the FDA now looking into a link between Stalevo and prostate cancer?
SB: The systematic look at the safety of Stalevo came out of the STRIDE-PD study, a very large randomized controlled trial looking at whether this medicine would be good for Parkinson's patients in terms of reducing fluctuations that lead to dyskinesias. When the researchers looked at all types of adverse events in this trial, they found an increased risk of prostate cancer in the group taking Stalevo versus the group taking Sinemet.
MJFF: How does this new information affect patients currently taking Stalevo?
SB: There are really two issues. For one, I think most Parkinson's patients will be judicious switching to Stalevo or adding COMTan. Not that we won't use these drugs but we will be stricter in terms of indications and whether we really think the patient will benefit from the addition. Once these drugs are added to a drug regimen, we'll be checking to make sure it's really benefitting the patient. Plus, we'll be a little more vigilant in terms of prostate cancer. Basically, we'll continue taking care of our patients while making sure the men go get their PSAs and see their internist and urologist.
But it's important to remember that Stalevo is only under investigation at this point. The FDA is pulling together the data and looking at a lot of different studies involving Stalevo or COMTan, and hasn't come out yet with a decision. For patients, particularly males, who are doing well on Stalevo, I don't think physicians will take them off of it because of the investigation. Instead we'll just continue to monitor the prostate and see what the FDA decides. For other patients who are on Stalevo and maybe not be benefitting clearly from it, there may be a more critical look, weighing the plusses and minuses.
MJFF: What about other cancers? Has Parkinson's treatment or Parkinson's disease itself been linked to other cancers?
SB: I'm sure the FDA is considering risks for other cancers as well and surveillance going forward in all of these drugs. We've actually been looking at cancer risk in Parkinson's patients for years, particularly skin cancer and melanoma. First, are Parkinson's patients at increased risk of melanoma, and second, is it due to Parkinson's disease itself or related to the treatment of Parkinson's? This debate is still ongoing in the community. And if there is an increased risk of melanoma, is it across the board in all populations with Parkinson's? Is it true for genetic forms of Parkinson's as opposed to non-genetic forms? Are men and women equally at risk? And then looking at the various cancers -- prostate cancer, breast cancer, etc. -- are there specific cancers linked to Parkinson's? There's been a long interest in the association between cancer and Parkinson's, in both directions with some studies showing a lower risk for non-melanoma cancer. It's a really interesting piece of the Parkinson's story that remains to be fully explored.
MJFF: Can you talk about how Parkinson's or Parkinson's treatment could lead to an increase in melanoma? How does this affect treatment decisions?
SB: L-DOPA is needed to make the skin pigment melanin. So it makes sense that if you introduce excess L-DOPA into the system or hype up the system in any way, you could increase risk for melanoma. The usual precaution a neurologist would take for a patient with a history of melanoma is to be cautious about treatment with dopaminergics although the most recent studies find that the risk is not from taking the dopaminergic drugs but having Parkinson's.
Because the risk appears to be related to having Parkinson's we also need to be careful with all of our Parkinson's patients in terms of skin cancer. We need to more routinely ask our patients to have a yearly body check and to look for any abnormalities on the skin. We've been thinking of developing a booklet for patients, to help them keep track of cancer checks and remind them to ask, "When was the last time I saw a dermatologist to just to look at my skin even if I don't have a specific problem?"
MJFF: So basically, the message to patients is to just stay vigilant.
SB: Yes, stay vigilant and keep track of your overall health. I think the overall message about Stalevo is that we still don't know if it really increases the risk of prostate cancer. So for me now, when I see patients, I'm just a little more conservative. Is it really needed? If I've added it, is it really helping them? And if it's really helping them, and their quality of life and their day is better, we tell them about the potential increased risk of prostate cancer and weigh the risk versus the benefit. If it's really helping, we'll wait to see what the FDA says.