Self-Management Strategies for Peripheral Neuropathy: A Breast Cancer Awareness Month Interview With Connie Visovsky, PhD, RN, ACNP, FAAN

Oncology Data Advisor: Hi, and welcome to Oncology Data Advisor. Today, in honor of Breast Cancer Awareness Month, we're having this interview with Dr. Connie Visovsky. Thanks so much for coming on today.

Connie Visovsky, PhD, RN, ACNP, FAAN: Thank you for inviting me. I'm very excited to be here with you today. As you said, Keira, I'm Connie Visovsky. I am a Professor and the Hughes Endowed Chair in Nursing Science at the University of South Florida in Tampa. I've been studying peripheral neuropathy, it almost seems like my whole life, but I want to say since a little before the year 2000. It's been a passion of mine for a long time. As a Nurse Practitioner for many, many years, I saw patients have peripheral neuropathy that have to live with it over time. We saw them go from perfectly functional people to having trouble with their activities of daily living and quality of life. That really struck me because as a Nurse Practitioner, I saw patients in more of the acute care setting. But when I started seeing people in follow-up, that's when it really hit me how much peripheral neuropathy impacted their lives.

Oncology Data Advisor: Like you said, peripheral neuropathy is a significant issue in breast cancer, and I know you've done a ton of research surrounding it. What is some of the research that you've conducted or that you're currently working on surrounding this?

Dr. Visovsky: In the past, I've looked at non-pharmacological ways of helping patients to manage and self-manage their neuropathy. Everything that I saw published in the scientific literature in terms of prevention and treatment of neuropathy using pharmacologic agents was either contradictory, had mixed results, or totally failed. So, what did we have to work with for patients? I began to explore the idea of using exercise because I was really interested in helping patients maintain physical functioning.

I did a study with 19 women who had breast cancer and were undergoing chemotherapy. I started the study when they began their taxanes. They had already gotten doxorubicin and cyclophosphamide and they were beginning their taxanes. I followed them and gave them resistance exercises for the lower extremities to do at home. We had a very positive outcome, but what I found out was that it was difficult for patients to manage the side effects of therapy. At that time, they were given dose-dense taxanes, so every two weeks, they were coming in for their taxanes. Those toxicities added up quickly, and patients had difficulty maintaining exercise in the right dose and the right intensity.

I learned a lot in that study, and now I have transitioned. I have a large National Cancer Institute–funded study looking at using gait, balance, and resistive exercise, still focusing on the lower extremities because it's my belief that's what keeps you independent. We are recruiting women now for that trial. They get the exercises or they get an attention control. It's a 16-week study, and our outcomes that we're measuring are sophisticated measures of gait, balance, neuropathy symptoms, nerve conduction, and nerve biopsy, so looking at intra-epidermal nerve fiber density and muscle strength and quality of life. Those are our outcomes, and we're still recruiting for that study. It's here in Tampa, Florida.

Oncology Data Advisor: That's definitely an amazing study and very needed. You mentioned some of the additional self-management strategies for CIPN. Do you have any other advice for women who are experiencing this, about how they can help to self-manage it?

Dr. Visovsky: I do. We know that neuropathy is causing toxic damage to the peripheral nerves by the chemotherapy agents themselves that result in these neurotoxic symptoms. These symptoms are sensory in nature, so numbness, tingling in the hands or feet, and motor symptoms that include motor muscle weakness and muscle wasting. There are autonomic symptoms where people can drop their blood pressure from lying to standing and can experience sexual dysfunction and gastrointestinal problems. This occurs in about 60% to 80% of women who receive taxanes for chemotherapy. The more exposure you have to these therapies, as I mentioned with the dose-dense therapies, the higher the severity and the longer you have those symptoms.

In 2020, the American Society of Clinical Oncology (ASCO) published their clinical guidelines. They have no recommendations for prevention of chemotherapy-induced neuropathy, and only duloxetine is supported for decreasing neuropathic pain. There is limited and contradictory evidence for things like anticonvulsants such as gabapentin, pregabalin, tricyclic antidepressants, and topical lidocaine. We really want to avoid at all cost opioids, which are inappropriate for neuropathy.

In terms of non-pharmacological therapies, there was a 2022 publication, a systematic review and meta-analysis that looked at some non-pharmacologic therapies that patients could engage in. It found that the most beneficial effects were seen in exercise. But I will tell you there are some benefits to acupuncture in terms of pain relief, in massage of the lower extremities and the hands, and in foot baths. In fact, we do hypothesize that, especially with the taxanes, neuropathy is caused by damage to the mitochondria, which is the energy-producing part of the cell, and also by the drugs actually reducing blood flow to the peripheral nerves. By giving a foot bath, a warm foot bath, you can increase blood flow to the peripheral nerves. And that's what I postulate that exercise does.

The European Society of Medical Oncology also did an exploration of this, and they found that exercise actually had level one quality evidence. Some of the studies were also mixed, and these are mostly because of bad study designs, quite frankly. In self-management, exercise remains the most studied self-management strategy with the most evidence. That 2022 publication I mentioned earlier, which was a systematic review and meta-analysis that looked at 13 studies, found the strongest evidence for physical exercise to reduce neuropathy severity. One study even found positive evidence for glutamine supplementation. Again, we still need lots more work in this area before we can say there's any kind of gold standard recommendation.

Oncology Data Advisor: Great, those are definitely some really useful strategies that are valuable to share with our audience. In light of October being Breast Cancer Awareness Month, do you have any messages about CIPN and awareness of it that you'd like to share, either for patients who are experiencing it or for nurses and physicians who are managing it?

Dr. Visovsky: Absolutely. I think that in terms of patients, let's be aware that it's going to happen. It usually starts to happen by the second cycle of a neurotoxic chemotherapy. We want patients to monitor themselves for changes in their function and changes that include pain. You can obviously have neuropathic pain, you can have hypersensitivity—even the slightest touch or the feeling of sheets on your feet, for instance, can cause discomfort—numbness, tingling, and loss of sensation so that you have altered gait imbalance, which is actually why we're studying it. Awareness and education are really paramount.

For the providers and for nurses who are taking care of patients, again, monitoring them from baseline is important because people come to cancer with all kinds of preexisting conditions. For instance, you can have neuropathy from diabetes and then go on to have a cancer which you are going to have neurotoxic chemotherapy from. Monitoring is really important in telling patients what to report. Then providers should stay away from these non-proven therapies, therapies that are not evidence-based, because they cause a great deal of frustration in patients. We almost try anything and throw anything we can at them with the best heart because we want to help patients, but going from one therapy to another to another is very frustrating for patients. So, let's stick with those evidence-based therapies.

Oncology Data Advisor: Great, thank you. That's really helpful to know. My last question for you is a little bit of a different topic, but going back to our ODACon Breast Cancer Conference from last year, have there been any recent updates on the topic that you presented, which was CDK inhibitors, or new strategies for managing their use?

Dr. Visovsky: Yes, so we know there are three CDK4/6 inhibitors right now—palbociclib, ribociclib, and abemaciclib—and there actually have been really no head-to-head comparisons between these agents. Right now, there are phase 3 trials that are in effect looking at these agents in both the adjuvant and neoadjuvant setting. There are also studies looking at biomarkers. One of the new things is we expect to see resistance to CDK4/6 inhibitors just like we have to other chemotherapies. There's a need for prognostic biomarkers to further refine treatment. In other words, if in some patients they have more increased activity to the CDK-RB-E2F pathways that actually predict sensitivity of tumor cells to CDK4/6 inhibitors, we would use them more in those patients. So, we're looking right now at biomarkers.

The other new direction is looking at therapeutic drug monitoring. For many drugs, there is a therapeutic index, so we monitor serum levels or plasma levels of those drugs. Those plasma concentrations usually have a predefined window. Well, we just don't have that for CDK4/6 inhibitors, and having that would be helpful in improving treatment outcomes and decreasing toxicity. Right now, that's also something that's needed and a new direction.

We also are now looking at increased applications of CDK4/6 inhibitors in human epidermal growth factor receptor 2 (HER2)–positive breast cancer patients, because there's some kind of crossover between those HER2-negative and HER2-positive patients that they may benefit from these drugs. We're also looking at the use of CDK4/6 inhibitors potentially in patients who are triple-negative, and also combining those CDK4/6 inhibitors with chemotherapy. And of course, in the pipeline are several new types of CDK4/6 inhibitors. So, we'll stay tuned for all those new developments.

Oncology Data Advisor: That's great. It's exciting to hear about all those new directions and to hear about your research in CIPN as well. Thank you so much for coming on today to share all this information.

Dr. Visovsky: Thank you, Keira. Thank you so much for inviting me, and I wish everyone a wonderful day. Take care now.

About Dr. Visovsky

Constance Visovsky, PhD, RN, ACNP, FAAN, is the Director and Lewis & Leona Hughes Endowed Chair of the College of Nursing at the University of South Florida. She specializes in the treatment of patients with breast cancer, with noted expertise in the management of neurotoxic effects of chemotherapy, particularly chemotherapy-induced peripheral neuropathy. Dr. Visovsky's research interests include exercise behavior and gait and balance training for improving symptoms of neuropathy in patients receiving chemotherapy for breast cancer. She has authored or coauthored numerous peer-reviewed publications focused on nursing management of patients with cancer.

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Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.