Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers Guideline Update

An interview with Dr. Charles Loprinzi from Mayo Clinic in Rochester, MN on "Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update." This update incorporates new evidence into recommendations for the prevention and treatment of chemotherapy-induced peripheral neuropathy in adults with a history of cancer. Read the full guideline at www.asco.org/survivorship-guidelines

TRANSCRIPT

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Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org.

My name is Brittany Harvey, and today I'm interviewing Dr. Charles Loprinzi from the Mayo Clinic in Rochester, Minnesota, lead author on prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers, ASCO guideline update. Thank you for being here, Dr. Loprinzi.

It's my pleasure to participate.

First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each of our guidelines. The full conflict of interest information for this guideline panel is available online with the publication in the Journal of Clinical Oncology. Dr. Loprinzi, do you have any relevant disclosures that are related to this guideline topic?

Well, that's always the perception, I think. Let me mention a couple of things. I've been intimately involved with research with chemotherapy-induced neuropathy for about 20 years or so, and have looked at a lot of the different drugs and treatments that we considered in this guideline.

I consulted for companies that have interest in neuropathy, including Asahi Kasei Pharma, Disarm Therapeutics, Metis Pharmaceuticals, PledPharma, and NKMax America. But other than that, I do not have anything else to note there.

Great, thanks. So first, what prompted an update to this guideline on the prevention of management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers?

Well, it's been about five years since we did the initial guideline. It is a very prominent problem-- I think probably one of the most prominent chronic problems we get associate with chemotherapy. You get acute problems like nausea and vomiting, but those go away. But this can be a prominent problem that can last for years.

There have been about 40 new trials for looking at prevention of neuropathy while you're giving chemotherapy, or treatment of neuropathy after you receive the chemotherapy and looking at ways to try to treat that. About 40 new trials have been published since we did the last guideline. So it was decided that it's time to look at this again to see what's new, what's not new, and sort things out.

So with that new information that the guideline panel looked at, what are the recommendations for prevention of chemotherapy-induced peripheral neuropathy?

OK. So for prevention-- and we're talking about you're about to give chemotherapy that has neurotoxic properties, if you will. Not all chemotherapies cause neurotoxicity. And by neurotoxicity, I'm talking about numbness, tingling, pain, usually in distal extremities. Hands and feet is where it usually starts. But that's what we're talking about here.

And the bottom line answer, which is similar to what it was five years ago, is that there is no proven means for being able to prevent this problem other than not giving the chemotherapy that can cause the problem. And we usually want to give the chemotherapy to try to kill the cancer process. So there is no proven means.

There is, however, suggestive evidence for a few things. And each of these need more research to really clarify the risks of doing them and that benefits from. One of these things is something called cryotherapy or cold therapy. And you put cold therapy on hands and feet, causes less blood flow, and slows the metabolism somewhat while the person is getting chemotherapy. And there's suggestive evidence that helps, although not proof.

There is another thing that's somewhat related to that, and it's called compression therapy, where if you put tight surgical gloves on a hand while you're getting the chemotherapy, decreasing blood flow when there's a lot of chemotherapy in the blood-- again, suggestive evidence. But there is things where they've actually combined these things with both doing cryotherapy and some compression.

And the third thing is exercise. There are data suggestion that exercise can decrease the amount of neuropathy that patients get. Again, no proof for any of those three things, but more research is needed in that area.

Thanks for reviewing those recommendations for prevention. What are the recommendations for treatment approaches for chemotherapy-induced peripheral neuropathy?

So I think we have two things in here. One of them is what about when you're giving chemotherapy to a patient-- neurotoxic chemotherapy-- and you're planning to give, let's say, 12 cycles of paclitaxel, a common drug that we give for 12 cycles once a week-- one-week cycles, so dose once a week for 12 weeks, and it causes neurotoxicity. And you might be six or seven or eight doses in, and the patient's getting fairly significant neuropathy. And you're worried about giving more of that chemotherapy because it might cause more neuropathy, which may not go away for months or years after it is finished.

So in that setting, the decision, the recommendation, is for the doctor to think about how much additional benefit are we going to get from continuing onto the 12 cycles from the 8 cycles or 6 cycles wherever we are, and decide how much, if this is given in the adjuvant setting where you're trying to cure a person.

They've had surgery. They've had-- the cancer has been removed, and you can see that there's a risk of recurrence, and you're giving chemotherapy to try to decrease the risk of recurrence, what percentage benefit will it get if you go on to 12 cycles? Is that 1% additional benefit that the patient wouldn't get recurrence? Or is it 10%? Is it 5%? Is a 15%? So helping to sort that through, and then talking to the patient about that, and then making a decision. Do I continue on with the planned full dose of their chemotherapy?

The other aspect is what about treatment of a patient who is finished with their chemotherapy, and now they have the neuropathy? And, again, for some types of chemotherapy drugs, their neuropathy continues to get worse for about three months after you've did the last dose of chemotherapy. It's not because you stop the chemotherapy that it makes the neuropathy get worse. But it's rather, in my mind, that it takes three months to get full manifestations of the neuropathy for drugs such as oxaliplatin.

So in that setting, there is one drug that is a winner, if you will, called duloxetine. It does improve things statistically significantly. It doesn't improve them a whole lot. But it does work, and it's been shown in repetitive studies for that. So that's the one recommended approach there.

There are three things where there is suggestive evidence of benefit. And, again, exercise fits in that category. There is some suggestion that patients who exercise will get benefit and get improvement. There are some data that acupuncture will cause some improvement. And there are some data that something called scrambler therapy, a type of cutaneous neuro stimulation process will help decrease neuropathy in those situations. Again, for all three of them, the committee was unable to say yes, we-- was unable to say that we have scientific proof that these work. But there's suggestive evidence that they might provide some benefit.

So with these updated recommendations, in your view, what is the importance of this guideline and its relevance for practicing clinicians?

I think it's-- again, it's a big problem in practice for patients-- oncologists as they're seeing patients, and for the patients themselves, and to find what we do know works, and what we know doesn't work, and what we think might be helpful is helpful for patients. It's helpful for patients to hear this and know this.

It's helpful for physicians to be able to say, yes, we looked at all the data. There were 42 more studies, and most of them didn't show benefit, unfortunately. Here's the ones that did show benefit, and here's the ones that are suggestive evidence, or some things like exercise is probably a reasonable thing to go with. Even though it needs more study, it's probably a reasonable thing for people to do, because we don't exercise enough in this country.

And then finally, you've touched on this a bit, but how will these guideline recommendations impact patients?

I think that just kind of as we said. You know, whatever the doctors can understand better about it, the clinicians there, and then relate that back to the patients themselves is the best way. Is it possible for the patients, and there are some very bright patients out there who could read the medical literature and take a look at this and read it on their own? Yes. Sure. Why not? But that's how I think. Understanding-- getting the physicians to-- scientists to understand what we do know, and then getting that word on to the patients and their families in this setting.

Great. Well thank you for your work on this important guideline update and for taking the time to speak with me today, Dr. Loprinzi.

You're welcome.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/survivorship-guidelines. This guideline also has a companion cancer.net podcast episode. Cancer.net is a patient information website of ASCO, and we encourage you to learn more by tuning into their episode.

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