10 hours ago
S3 Episode 2: Cancer Survivorship and Toxicities of Cancer Therapy
This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider.
Kathryn J. Ruddy, MD, MPH: Hello. I'm Dr Kathryn Ruddy. Welcome to season 3 of the Medscape InDiscussion Cancer Survivorship podcast series. Today, we'll discuss approaches to reduce the toxicities of systemic cancer therapy. First, let me introduce my guest, Dr Elizabeth Cathcart-Rake. Dr Cathcart-Rake is a medical oncologist at Mayo Clinic who specializes in the treatment of breast cancer.
Her research is focused on reducing symptoms in cancer survivors. For example, she's currently leading a cooperative group trial that aims to reduce chemotherapy-induced peripheral neuropathy to improve quality of life. Dr Cathcart-Rake, welcome to the Medscape InDiscussion Cancer Survivorship podcast.
Elizabeth J. Cathcart-Rake, MD: Thanks so much for having me.
Ruddy: I want to start by asking you about some of the most common problems among your patients due to systemic therapy.
Cathcart-Rake: We use a number of different systemic therapies, and each comes with its own side effects. There are side effects to chemotherapy, and these are fairly well-documented: things like fatigue, neuropathy, nausea, vomiting, alopecia, and risk of infection. There are also side effects to endocrine therapies, so our hormonal blocking therapies: vasomotor symptoms, hot flashes, night sweats, insomnia, mood changes, joint stiffness, and vaginal dryness. There are side effects to agents such as targeted therapies and antibody-drug conjugates, which are our newer medicines in the breast oncology space.
Ruddy: Immunotherapy has really revolutionized treatment in oncology. Are there specific side effects that you're seeing from immunotherapy?
Cathcart-Rake: Yes, absolutely. Immune-related toxicities can come up at any time, and there's a really broad group of side effects that fall under this bucket. It could be inflammation of nearly anything. So inflammation of the thyroid can cause thyroiditis or hypothyroidism, inflammation of the lung, pneumonitis, adrenalitis, hypophysitis, all those sorts of 'itises.' Many of these are managed with steroids and holding the offending agent. But these can also be really challenging.
Ruddy: Which of the chemotherapy side effects are we pretty good at mitigating, and which are we still really struggling to address well with evidence-based treatments today?
Cathcart-Rake: This is a good question because there's a group of side effects that we've gotten really adept at preventing and managing, such as nausea and vomiting. We have a number of antiemetics that we give as preventive medicines, and also for patients to take at the first sign of nausea. We know that growth factor support helps to decrease the length of time of neutropenia and neutropenic fever. And then we have strategies to help manage things like hot flashes and vaginal dryness. But even these strategies that have been fairly well documented, and for which we have a number of different medications to help manage, we still see patients really bothered by these side effects — so much so that with endocrine therapy, which is a pill a day for many patients, about 50% of patients stop their endocrine therapy early because of things like side effects. This is actually a huge number, acknowledging the fact that we have medicines and other ways to try to help manage side effects.
There are a number of side effects that we don't have enough research on, and we still don't address them well. We are hoping to help this with our own research, things like neuropathy. There's a single medicine that we know, that we've studied, that does help decrease the pain associated with neuropathy, but we don't have a good way to treat the numbness and tingling. And we don't have great prevention strategies other than changing the chemotherapy dose, which many oncologists and patients are understandably hesitant to do. Certainly, there's some interest in cooling, but the data have been mixed in clinical trials.
In addition to all this, there's a third group of medicines and side effects that haven't been well researched, that we don't have any active ways to manage, and that we need a lot more data to better understand.
Ruddy: One topic that is of a lot of interest to patients is scalp cooling. What are the logistics and the reasons that people might want to consider scalp cooling during chemotherapy?
Cathcart-Rake: Scalp cooling can help reduce the risk of hair loss and hair thinning during chemotherapy in particular. There are several different kinds of scalp cooling techniques. One is that big companies have scalp cooling devices in chemotherapy units. Patients typically will purchase their own, kind of like a hat that is fitted to them and they bring into chemotherapy, but they attach it to a machine in chemotherapy. There are other centers, though, that don't have access to those machines, and patients can buy these online and do the scalp cooling themselves. An organization called HairToStay, for instance, offers financial support for this kind of self-directed scalp cooling, which can be helpful. The Rapunzel Project is another one that can be really helpful for patients.
Scalp cooling can be really effective for some types of chemotherapy. For chemotherapy agents like Taxol, we see really high response rates where even 80% of patients can retain their hair. But there are other agents where scalp cooling is a little less effective. We're trying to get to the bottom of why that is, whether there are longer cooling times needed or maybe just a different mechanism needed, where we're seeing response rates even of 30% or so. None of these techniques is perfect. Some patients lose their hair, and this is also dependent on hair texture, race, ethnicity, and other factors. It can be a really great option for patients who want to retain their hair, particularly when hair is such a huge part of their identity. This can be hugely impactful in terms of quality of life.
Ruddy: Besides the cost, which I know can be substantial and the sometimes inadequate efficacy, are there any downsides to scalp cooling?
Cathcart-Rake: The cost is the big one. Logistics can be a real challenge. Even in places where you have a scalp cooling machine in the chemotherapy unit, it adds an extra couple of hours to your chemotherapy time. It's just a much longer day for patients, and you have to get the cap fitted correctly. There are a number of things patients need to do, including getting special conditioners, to help scalp cooling be as effective as possible. For patients who do this themselves, it's a big process. I'm so impressed with the dedication of our patients to doing these things that are important for them. Some of it involves checking the temperature of the caps multiple times throughout the chemotherapy infusion process. They'll actually switch out the caps when they get to be too warm, and they'll carry in these big chests of scalp cooling hats. It can be a big logistical challenge and a lot of added time and sometimes stress to patients and their caregivers who are going through the chemotherapy process, which is already time-intensive and unfortunately stressful as it is.
Ruddy: I've had some patients mention headache or the discomfort of having your head be cold, too. I don't know if you've seen that, but I have.
Cathcart-Rake: Yes, I'm glad you mentioned that. It's also the side effects of it. Unfortunately, there's no zero side effect option.
Ruddy: I want to talk a little bit about endocrine therapy. You mentioned some of the side effects of endocrine therapy, which is a very common treatment in patients with breast cancer and also some other endocrine-sensitive cancers. Can you talk a little bit about what evidence-based strategies we have for managing some of those menopausal-type symptoms?
Cathcart-Rake: Hot flashes are the first one that comes to mind. It's such a common side effect. Up to 80% of patients note some increases in hot flashes on these agents. There are a number of different strategies that patients can use based on the other medications that they're on and based on other symptoms they might be having.
I think of three big classes of medicines: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and oxybutynin. For SSRIs, I think of medicines like citalopram or escitalopram. I often lean on those agents when someone has concurrent anxiety or low mood associated with all of this, because these do help even out mood.
For SNRIs, I think about venlafaxine, which also helps with mood and anxiety. The one drawback of venlafaxine, and why I mention it after those SSRIs, is that it has significant withdrawal symptoms. Patients who aren't used to it or haven't been told about the withdrawal symptoms will sometimes stop it and not realize that they have huge rebounds and symptoms. They could have really racing heart rates, a significant increase in anxiety, and even some palpitations. Often we'll overlap that with an SSRI when we stop it.
And in this third group of medicines, one medicine is oxybutynin. This was initially looked at for bladder spasm, but it has been shown to help with hot flashes as well. That one's helpful if you have a patient who's already on a number of different mood medicines and you don't want to interfere with those or run into medication interactions. That one is not a great medicine to prescribe in older patients because they can feel a little dizzy or have some cognitive changes, even with that medicine.
Ruddy: These are very important issues. Please tell the audience more about your clinical trial through the Alliance for Clinical Trials in Oncology that is focused on chemotherapy-induced peripheral neuropathy.
Cathcart-Rake: We are really excited about this study. It's a cooperative group nationwide trial. There is an early-phase component and a leader-phase component where we are using a compound called ganglioside-monosialic acid (GM1) and looking into, first, the right dose, but then more importantly, the benefits of GM1 in preventing taxane-associated neuropathy, particularly with paclitaxel.
It is a prospective trial. We are administering GM1 intravenously (IV) prior to paclitaxel chemotherapy. We're giving patients this up to 12 cycles with their paclitaxel. The impetus behind this trial is that this compound had really significant improvements in terms of neuropathy prevention when it was studied in Asia. So, there are some really exciting preliminary data on this compound in other countries.
Ruddy: You've also done some very interesting work on nasal vestibulitis. Can you tell us what that is, and what might help patients with that?
Cathcart-Rake: Nasal vestibulitis is one of those side effects that is overlooked by a number of people because, honestly, it sounds like a silly thing. Nasal discomfort sounds like a little thing. But I have had very few other side effects that I've had so many patients send me emails about and say, this is a huge problem. In fact, this is like a million paper cuts, just on top of everything else. They have pain in their nose. Nasal vestibulitis is dryness. It can be crusting, scabbing, bleeding, and pain in the nasal passages. We have studied this prospectively. We see it associated primarily with paclitaxel, but also with Abraxane chemotherapy. We also see it with the vascular endothelial growth factor (VEGF) inhibitors, such as bevacizumab, at really high rates — like more than 70% of patients get the side effect. We've looked at a topical nasal preparation called rose geranium and sesame oil nasal spray; this can be compounded by any compounding pharmacy using pharmaceutical-grade oils, and folks can put that into their nose twice a day. We've shown that we can help treat these nasal symptoms significantly and better than we do with just nasal saline alone.
Ruddy: That's terrific. What about some of the rarer side effects — things like pulmonary, renal, and dermatologic toxicities? Can you speak a bit to those and how can we manage those?
Cathcart-Rake: The issue of a pulmonary side effect is really top of mind. Particularly because we're using so much in HER2 or fam-trastuzumab deruxtecan-nxki (T-DXd), particularly in the breast cancer space, pulmonary toxicity from Enhertu (T-DXd) in particular is so concerning because if left unchecked, if left unsurveilled, it can be fatal. Thankfully, that's very rare, but we can still see that. There are some consensus guidelines as far as surveillance monitoring with chest CT, for instance, and monitoring for symptoms. There's guidance both in the package insert and also by these consensus groups talking about managing primarily withholding the drug and steroids. That's a side effect that we've gotten some experience with over time, but there are many others that we're trying to learn more about and the dermatologic toxicities are of particular interest with a lot of our targeted therapies.
Things like capivasertib have a really high frequency of dermatologic side effects that haven't been well delineated. We often treat this the same way we treat most dermatologic issues: with topical steroids. But it would be great to have more information on who's at risk for that, and really what we should be using.
Ruddy: We used to think about hair loss as being specifically related to chemotherapy, but you're doing some work on hair loss as a side effect potentially of nonchemotherapy cancer drugs. Can you speak a bit about that?
Cathcart-Rake: We do see full hair loss with a variety of chemotherapies, which is a huge issue. But we're also realizing that a number of our endocrine therapies and targeted therapies also cause significant hair thinning and big changes in hair texture. We're seeing this a lot more now that we're prescribing more cyclin-dependent kinase (CDK) 4/6 inhibitors, such as ribociclib and abemaciclib in the adjuvant setting. We're seeing more hair loss and hair thinning with those. We're also seeing some of it with endocrine therapy alone — so tamoxifen and aromatase inhibitors (AIs), and this really hasn't been categorized as far as frequency and severity prospectively.
We have a prospective study where we're trying to quantify the number of patients who experience this and what patients are experiencing from a hair thinning perspective on endocrine therapy and CDK4/6 inhibitors. We're really hopeful that we'll be able to follow up with treatment trials looking into ways to try to help prevent this. Although hair thinning is milder than complete hair loss, these therapies continue for 2-3 years. For endocrine therapy, this is 5 years. So this is a long-term toxicity that can be really challenging for patients.
Ruddy: That is so important. How can we make sure that our patients know that we, as oncologists, want to hear about their side effects? Obviously, we can't manage them well if we don't know that somebody's suffering from something. How can we set patients up to know that we want to hear about that, and so that we can help them feel as good as possible during cancer treatment?
Cathcart-Rake: There are a number of ways to do this. Often in clinical trials, we ask patients about very specific symptoms, and we have very specific grading scales, which are really important. I don't advocate changing that. However, I also think asking open-ended questions is usually important — saying 'You know, if you could, bring up just one or two side effects that you feel like if we could change this, it would really change your quality of life in the course of this. What are those symptoms?' Something open but that gets to the heart and crux of the issue, which is, 'What are those things that are most meaningful to you that we could help with?' I think that can sometimes open the door for things that we're maybe not expecting or to hear more about, say, those nasal symptoms that people have. People might not bring up when you're asking these very targeted questions about things like nausea and vomiting.
Ruddy: Thank you so much for sharing your wisdom with us today. Is there anything else you want to tell our audience about before we close?
Cathcart-Rake: I'm so thankful for the opportunity to talk on this topic and to talk about some side effects that aren't mentioned as frequently in clinic visits. Especially if there are oncologists in the audience, I hope they'll consider enrolling patients in symptom control interventional trials and think more about these side effects and how we can better document them.
Ruddy: Thank you so much. Today, we've talked to Dr Cathcart-Rake about improving our management of side effects of systemic therapy for cancer. We've learned about some of her very exciting research pertaining to alopecia and chemotherapy-induced neuropathy, and her comments about symptom management in general were extremely informative.
Thank you for tuning in. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on cancer survivorship. This is Dr Kathryn Ruddy for the Medscape InDiscussion Cancer Survivorship podcast.
Listen to additional seasons of this podcast.
Patient-Reported Discontinuation of Endocrine Therapy and Related Adverse Effects Among Women With Early-Stage Breast Cancer
Scalp Hypothermia to Reduce Chemotherapy-Induced Alopecia: A Systematic Review and Meta-Analysis
HairToStay
The Rapunzel Project
Scalp Cooling for Hair Preservation and Associated Characteristics in 1411 Chemotherapy Patients — Results of the Dutch Scalp Cooling Registry
Advances in the Management of Menopausal Symptoms, Fertility Preservation, and Bone Health for Women With Breast Cancer on Endocrine Therapy
Venlafaxine Withdrawal Syndrome
Oxybutynin vs Placebo for Hot Flashes in Women With or Without Breast Cancer: A Randomized, Double-Blind Clinical Trial (ACCRU SC-1603)
Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II)
The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients With Breast Cancer: A Randomized Trial
Nasal Vestibulitis: An Under-Recognized and Under-Treated Side Effect of Cancer Treatment?
Multidisciplinary Clinical Guidance on Trastuzumab Deruxtecan (T-DXd)-Related Interstitial Lung Disease/Pneumonitis — Focus on Proactive Monitoring, Diagnosis, and Management
Retrospective Cohort Study of CDK4/6-Inhibitor-Induced Alopecia in Breast Cancer Patients
