 All right, and then our very last formal talk today is by Sarah Yenzer, what he comes to us down the street from Duke to talk to us about managing some of the side effects of kidney cancer treatment. Hi. I'm a nurse practitioner at Duke. I've been there for 12 and a half years in this role and I love it. It's probably my favorite thing is managing side effects and I think it's a really important role that the APPs, meaning the nurse practitioners or physician assistants in your clinic can provide you. Physicians often do a good job of this as well. I'm not saying they don't, but this is a bit more my focus than just thinking about disease and what's going on. We have to figure out how to get you through the disease and how to get you through the treatments so that you can live a good life while you're taking these drugs that can sometimes make you feel crummy. So I usually like when I'm teaching anybody about the side effects, I like to talk to people about the side effects by class because I think it helps you remember, if it ends in this, these are the likely side effects that are going to happen. Now, this is like a big broad things that can happen. So fatigue, thyroid problems, cardiac side effects usually like congestive heart failure type things or increased risk for heart attack, elevated blood pressure, nausea or stomach irritation, diarrhea, rash, hand foot, mouse orness, taste changes, and some of them cause heron skin changes, which we'll talk about in a little bit. So those are what we call TKIs or tyrosine kinase inhibitors and they end in nib. So mTOR inhibitors are like the Everolimus, Temserolimus drugs using them not as often now, but they are still used the Everolimus typically in combination. Temserolimus is indicated for like porous patients, but again, we're not using it super often anymore. The things to think about with this are fatigue or ulcers, taste changes, low-foss, it can elevate cholesterol and blood sugar, decrease your kidney function over time. That does go away if you stop the drug, nausea and stomach irritation, diarrhea, rash, pneumonitis infection. It's kind of a general overview. So we're going to talk about these two first, and at the end we're going to talk about the immunoncology drugs that we're using. So diarrhea, super common pretty much with every mTOR TKI. When you read something about diarrhea, it will always tell you to make dietary changes. So you should eat less dairy, you shouldn't eat fried foods, you should stay away from anything that can make it like high-fiber diet, that sort of thing. Sometimes though, that doesn't work so well with people who have cancer, because sometimes the only thing that tastes good is milkshake, and so am I going to take a milkshake away from this patient to control their diarrhea? No, I'm not. I'm going to control their diarrhea. So I think using Emodium and Lomodol are really important. I use Emodium usually in patients who have just random diarrhea throughout the day. It's a good place to start. But if you eat and then immediately have diarrhea right after, Lomodol is probably the best drug for you, because it's going to slow down the peristaltic movement. So your bowel going crazy, it's going to slow that down so that it doesn't happen as frequently. So those are the two drugs we usually use, and sometimes we use them in combination. A dose reduction is also a valid form. Like if we're trying the Emodium or trying Lomodol, that's not working. We need to talk about dose reductions. So I'm going to take a minute to talk about dose reductions in general, because I think that patients are afraid of dose reductions. They want to get the biggest dose possible so that their cancer is gone after at the highest way possible. So when we pick the doses for drugs, that's done by clinical trial. And even in those clinical trials, patients are reduced for their dose. What we don't know when we give you the drug is how it's going to affect you personally. So some people get rid of the drug really fast, meaning their body metabolizes it really quickly. And so they have hardly any side effects on a maximum dose. There are other people though that bodies like to hang on to the drug and they don't want to let it go. And so if you read like the package insert with all the possible side effects, that person might get it from the same dose that somebody would be like this is no problem on. Because their body likes the drug and holds on to it, won't get rid of it. And so as a result, the right dose for everybody is not necessarily the first dose that you start on. At Duke, we do like to start high. So we will start at the recommended dose and then go down from there. The only situation where we do not do that is in people who have previously shown that they do not tolerate a certain sort of drug. So let's say somebody had been on Suthent before and they did terrible with it. And we try, you know, like we had to dose reduce them. Maybe there were 25 milligram patient, 50 milligrams usually the starting dose. And then let's say we gave them ExitNib, we gave them five milligrams and we had to dose reduce that as well. If I give them another TK, I'm not starting at the top because if I do, I know that they're gonna end up in that exact same situation because they are people who are really sensitive to TKIs. So those are the things that you have to think about. You know, it could be a really tall man. It could be a really big person. Honestly, most of the time it's tiny white women who do not tolerate the TKIs very well. So those are the sorts of people that I really take a close eye on when it comes to taking drug and dose reductions. The other thing about dose reductions is that it is sometimes what's necessary for you to have a good quality of life. So does it matter if we totally bash down your cancer but you feel horrible and can't get out of bed? Is that how you want your life to be? And if it is, I'll work with you, you know, that's great but we need to have the conversations like what do you want your life to be like? Do you want to be out and doing things? If you do, I wanna make sure that we're managing things properly and we drop back on those doses. So that is my plug for dose reduction if needed. For nausea, a lot of times people will say their stomach's upset and it's not conventional nausea in the TKIs and the mTOR inhibitors. Typically it's a gastritis type situation. So we're using a lot of H2s which are like Zantac or Pepsid or proton pump inhibitors which would be like Prilosec, Nexium, those sorts of medications. Now there was a trial that came out stating that when you use these drugs in combinations with Votrient it decreases the amount of Votrient that's in the system. So we do try to use them away from when people take drugs. However, that trial came after their approval. The approval happened with patients who were on H2s and PPI's. And the reality is either you're gonna get it or you're gonna just reduce, especially if somebody's not eating. So I continue to use H2s and PPI's in these patients despite that. Composine is also another drug that we use fairly frequently. Typically people think oh I should give them Zofran but often that's not a medicine that will really work fabulously and it can be a little bit more expensive. The H2s and the PPI's typically work really, really well with people who are on these medicines. And then the next one is fatigue. So when you think about fatigue, first of all you wanna make sure that there's no other reason that it's happening. Is someone really anemic? Do we need to give them iron or B12 supplementation? Do they need blood? If those things are happening, obviously that's more likely the cause than the medicine. If you're on a TKI, so like any of those Nib drugs, you think about the fact that they can affect the thyroid. So sometimes you could have some thyroid dysfunction. It's really important that we're checking for thyroid dysfunction at least every three months. We try to do it every six weeks in our practice. And we treat people when we're noticing that the TSH is elevating and the T4 is down. So very often the T4 or the TSH which is the thyroid stimulating hormone will go up quickly and primary care doctors might see that and say oh we need to treat somebody right away with some Synthroid. If we do that though we can make people hyperthyroid rather than hypothyroid. So when you're hyperthyroid that causes a lot of palpitations and can make you feel anxious. I had one guy who this actually happened to. His primary care doctor had given him some Synthroid for an elevated TSH without checking the T4. And he came to me unable to sleep. He said I'm really anxious. I'm having all of these palpitations. I checked his labs and he was hyperthyroid at that point. So we need to stop and pull back on that medicine. So again what I usually do is as I see that going up I watch the T4 and as that goes down if it's getting closer to the lower end of normal or below I'll start with a really small dose and see what we can do to kind of keep that under control. But I always start low and go kind of slow with that medicine because it can quickly flip the opposite direction. So that's the thyroid. Are people sleeping? It's something that isn't always asked but are you sleeping or having to get up a lot at night to go to the bathroom? What's going on with your sleeping? Are you napping during the day? What's your nutritional intake? If you're not eating you're not gonna feel very good. You're not gonna have a lot of energy. Also what have you been doing lately? We really try to encourage patients to walk about 20 minutes a day if you can to keep your energy up throughout treatment because that is a really good way to combat fatigue. So if you're able to walk about 20 minutes or do some sort of exercise, even swimming it can really be beneficial to you over the long run. So if all of those things are no like everything else is perfect then we blame the drug. So I don't usually blame the drug first. I make sure everything else is okay. If everything else is okay then it's the drug and if it's significantly affecting your life that's when we would talk about a dose reduction for fatigue. And by significantly affecting like can you get through a shower? If you can't get through a shower you definitely need a dose reduction. If you can't make it around the grocery store we should have a conversation about like what are your goals and how should things be should we dose reduce. So that's just a little bit about fatigue. I went the wrong way. Oh, hypothyroidism I already ranted about. So like I said we try to check it at least every three months but typically I end up checking it about every six weeks. High cholesterol and triglycerides typically happen with the mTOR inhibitors. We do medications to treat that and some dietary changes if appropriate. Cause again, only certain things taste good right? So do we need to mess with your dietary stuff or could we just treat it and move on? So I try not to mess with people too much if at all possible. These I have a policy in my clinic that if I broke it I fix it. However, like if I give you this drug and it increases your cholesterol that's my problem. But if you do have a primary care doctor or a cardiologist that you work well with and things have been going well with I'm happy to work with those people to manage things but also I just have the policy if I broke it I'm gonna try to fix it. Low phosphorus is pretty common in mTOR inhibitors as well. We do dietary supplementation and sometimes medications for that. Having a low phosphorus actually makes people tired. They feel kind of crummy and it's kind of a weird tired. So that's one thing to look out for for mTOR inhibitors. But also if you're on a bone agent in combination with an mTOR inhibitor or TKI like you're thinking Zomeda or Exjiva. So something that could be used to strengthen the bone or prevent bone breakdown. Those medicines also can decrease your phosphorus. So that's a good thing to keep an eye on as well. So rash, typically the rash happens in mTOR inhibitors. They can occasionally happen in TKIs. We don't typically see them that often but it's really more of an mTOR inhibitor. Sterids can be helpful if you apply them directly. Obviously avoiding fragrances and lotions. It's possible it could require a dose reduction if it doesn't go away. We were using mTOR inhibitor for prostate cancer in a clinical trial and I had a man who came in about a week or two into his first round of medicine and he was covered from head to toe in this rash. It was phenomenal and it actually lasted three months after he was on treatment. Again, we were not using it for kidney cancer. I have not seen that in kidney cancer but it was a pretty dramatic rash for that particular patient and it took quite some time to reduce it. So he did actually have to get oral steroids and he was with dermatology and they took care of him for us. So like I said, it could require a dose reduction. Medication for itching is helpful like Adarax but it'll also make you a little sedated so there's kind of a balance there. So hand foot syndrome typically happens with TKIs and it's typically in areas where you have a lot of what we call microtrauma. So places where you rub a lot. Let's say I have a Diet Coke addiction. So when you're constantly opening and closing that you can get spots on your hand here and here even from a water bottle or whatever. So that repeated use of the same things can really give you areas where you have issues. If you wear tight shoes or even just any shoes where you have a specific spot where your feet rub. I had a patient who worked in a factory and her job was to carry these metal tubes from one place to another place and she had it really bad across like the ball of her hand and the bottom of her hand where that rested. I had another man who was a truck driver and he got it really bad on his fingers and the palm of his hand from gripping the steering wheel all day. So what we did for him was obviously using the thick lubricants really good. Using a steroid on that is helpful as well but gloves while he drove helped a lot in preventing that repeated trauma and he did a lot better once we switched over to that. So those are things we do. Protection being like gloves, if you're a gardener you wanna be using gloves. I had a lady who was an advent knitter and she had the, her hand foot was like right here in her hand and on her thumbs where she held her needles and then around her finger where she held tension on the yarn and it was just from constantly doing that knitting that she had those spots in exactly all of those places. So we had her take a quick break and then once she was healed up she wore gloves while doing it which made it a little bit better but according to her very difficult to get done but it was helpful. So like I said, steering creams we use as well and especially in clinical trials we had patients who were on some pain medicines like the last couple of weeks of being on a drug before they took their break. I had a lady who was a trial lawyer so when she was in a trial, she had to take narcotics to keep her feet under control because she had to stand a lot and she would not disreduce. We had a conversation about that, she would not. So that was kind of a difficult situation. I did happen on to another thing that we've been trying with patients from a wife, a patient's wife. So I have a patient whose wife is this amazing old nurse like a hardcore old school, 80 year old nurse and she said, I fixed his feet when she came in to visit me. I was like, really, how'd she fix his feet? She's like, well, you know, my knees are bad and I've got this Voltaren gel at home and I decided that we would just try it on his feet and it actually did completely heal his feet. So I've used it on some other people with some success. Obviously, I think we need to do a clinical trial before I would say officially that's the best thing ever but Voltaren gel is something that works or has worked in my practice. So something to think about. These are pictures of what hand foot syndrome can look like. It's really important if you're having like a buildup of houses or sore spot on your feet or hands that you show them to your provider. Don't try to be strong, don't be tough. We really want to see what's going on. I had a guy whose feet were looking a little rough when I saw him but wasn't at a stage where I needed to hold his drug or stop anything. But I let him leave me for two weeks and when he came, well, I got a phone call from his wife that said, I really think I need salivating cream. So I don't know if any of you know what salivating cream is but it is for burn patients. We put it on burns a lot. And I was like, you need salivating cream? She's like, yeah. I was like, how about you come see me instead and we'll have this discussion. So basically when this man came in, despite the fact that he had been told that this could happen and he needed to let me know if things were getting worse, he looked like he had stuck his feet into like oil, like hot oil and his skin was just like off and he had burned areas. It was horrible. So the fact that he hid this from me resulted in him being off drug for about two months because he was not able, like we had to wait for his feet to heal. It was so bad. So it's really important that you tell us early. I mean, obviously I knew what was going on with him but he was a little stubborn and he would, he lied to me and so as a result, he had to send us pictures, like take pictures of his feet and email them to us every two days because he wasn't allowed to be by himself on drug. So blood pressure medicine. So blood pressure problems are really common just to begin with. So before we put you on any drugs, we should try to optimize your blood pressure. Then once you go on drug, it's likely that your blood pressure will go higher, especially if it's a TKI. So when I look at that, we keep an eye on what's going on. I usually have people back about two weeks after they start medicine. And if we're seeing that it's going up, we need to get going on a medicine. I think about what else is going on with them. Like, are they diabetic? What else is happening when I start their first medicine? Honestly, it's rare that I'm starting somebody on their first medicine. Usually they have other medications. I will go to three medicines but at three you get to go see the cardiologist. We are lucky though. We have an oncology cardiologist at Duke who helps us out a lot with this sort of stuff and with management. But again, this is another situation where I broke it. I try to fix it unless it's out of my league and then I'll send you on. Or unless you have a really great doctor that you are very happy with and things are going well, then we'll work together to make sure we manage you properly. Diuretics are typically not a good choice for patients. Lasix or hydrochlorothiazide I try not to do for treatment of hypertension. And the reason I don't is because typically patients on these medicines have one kidney. So you're already down one, right? You have a potential to get nausea, vomiting and diarrhea which could potentially dehydrate you. So that plus a diuretic I don't think is typically a good idea. So unless you've already been on it I'm not likely to give it to you. And then monitoring is just really important. If you can keep an eye on your blood pressure at home and then we'll check it when you come into the office as well. Sometimes the office is not the best place to be the only place you get your blood pressure checked. So in my clinic, you've already dealt with the parking deck which is horrible or the valet which is also horrible. You've been to the lab which is quite a wait. You come upstairs and if you're seeing me maybe I'm on time if everything's perfect but if you're seeing my boss, he's not on time. And it's possible that it might get a little frustrating sitting out there. So, and you're coming to talk about your cancer. So it's not exactly the best least stressful place for a patient to check their blood pressure. I think it's important that we are checking it there so we could see what's happening kind of in the pressure cooker type situation. But if you're a little elevated with me but at home you run in the 110s, 120s, I give you another medicine for your blood pressure. You could pass out, you could fall down, you could hit your head. There are a lot of things that could happen that are negative so we have to be really careful when managing that that we're not over managing. Obviously if you come in with a blood pressure 180 you're unlikely to pass go. Like you're gonna get something for me. But if you're in the 140s, 150s, that's more of a conversation. So hyperglycemia is typically happens in the mTOR inhibitors. We also do see it sometimes in the immunotherapy drugs that we're using. Dietary changes again are really difficult because when you're on the TKI's or the mTOR inhibitors, food tastes very differently. For most patients, meat does not taste good. Like a lot of over-enriched bread products or cereals often taste very minerally to patients. Not everybody, but a lot of people. Green vegetables taste very minerally to patients so they're not necessarily up for it. Usually what tastes good are beans, pasta, carbure vegetables, fruit, sweet things. Sweet things, really. Sugar, right? Anything sugary. Cake, pie, so when you have hyperglycemia and your taste is horrible, we need to really try to more aggressively manage your blood sugar than manage your diet because a lot of people will not eat and will lose weight during this time if they're trying to manage it strictly with diet. So that's just one of those things we kind of keep an eye on and start orals early if we need to. If it happens on immunotherapy, though, it's likely because of inflammation of the pancreas and we typically have to give you insulin. The oral therapies will not work. It's another situation where coordination of care is important. I broke it, I fixed it, but if you have someone that you work with, typically we would wanna work with them. If it's crazy and it's like beyond me, you'll see endocrinology as well. So mucosinus, this is like inflammation of your mouth, sometimes nose. This typically happens in both TKIs and mTOR inhibitors, but you're gonna see it differently in both drugs. That mTOR inhibitors, you see more oral ulcers than the other medicines where typically you just have tenderness of your entire mouth. Like, it feels like you sort of drink really hot coffee and now everything's pretty tender for most people if they get it. Toothpaste can be spicy for people, so we often recommend switching toothpaste to something a little bit more mild, like a biotean toothpaste, baking soda-based toothpaste, or like Tom's kid's toothpaste is really good. They have a strawberry variety that people think is awesome and it doesn't burn their mouth, which is really nice. And then from a mouthwash perspective, we want people to stay away from alcohol-based mouthwashes. So Listerine is not your friend when you're on these medicines. It will dry out your mouth and increase your risk of having the mucositis to begin with, but it'll also burn like nobody's business. So if you get the mucositis, so please stay away from alcohol-based mouthwashes. What we typically have people use are, again, the biotean is a decent mouthwash. I think it's CVS, carries a generic brand of biotean products that are really excellent and much less expensive. And then we also act, it has an alcohol-free mouthwash and Crest makes an alcohol-free mouthwash. So those are different options as far as mouthwash and toothpaste go. The saline rinses I think are really good from a preventative perspective. Just put a teaspoon of salt or baking soda, either one, and eight ounces of water, you can stick it right by the sink and swish and spit it like four or five times a day. That can kind of keep your mouth a little bit more normal. In clinical trials, that's actually been shown to be as effective as magic mouthwash for patients. Now magic mouthwash, everybody thinks is amazing. Sometimes it's not very magical, but it can be, it kind of depends. The good parts about magic mouthwash a lot of them have a little steroid in them which can be helpful for this mucosidus that people have. A lot of them have niestatin in them which is an antifungal medicine. I don't, you don't need that unless you have thrush in your mouth. So I usually don't give that to patients as part of a magic mouthwash if I do prescribe it. I usually like a malax benadryl combination maybe with his steroid. And then the gel clear I use typically for patients who have the actual oral ulcers. If you read the package, it's kind of expensive. I don't think insurance covers it super well. But if you read the package, it says to mix the whole pack with 10 milliliters of water and then swish it around your mouth and spit it out. And like one pack is one use. We don't do that at all because that's really expensive stuff and you don't want to waste it. So I had a brilliant patient who told me that she got her finger wet and put it inside the packet and then put it directly on the ulcer that she had and then didn't eat or drink anything for a half hour. And that actually did heal it up and restore it over a couple of days and she was in good shape after that. But she only used one packet over like three or four days rather than one packet three times a day. So that's just a little trick if any of you get into gel clear is to use that. So taste changes and anorexia are often also common. Like we had talked about earlier, sweets still taste the same. Most people need to avoid salty foods and sodas because they can be really rough on your mouth. The other thing that's difficult are like really crunchy things are really hard on your mouth. But some people I have one man who when he is like at the worst of his taste changes eats like fire wings from some restaurant. They just make him happy. I don't know, like I don't know how he burn, doesn't burn his mouth off, but he can sort of taste it. So that's what he's going for. So, you know, everybody's always different, right? For the taste changes, we do try zinc sometimes, 50 to 100 milligrams a day. Sometimes you can get a little bit more taste out of things if you do that. But it kind of depends person to person, how successful that's going to be. The other thing I always tell patients is to eat things they haven't eaten before. So fish and shellfish, seafood, usually taste the best of all meats for patients because it has a slightly sweeter undertone to it and it's not quite so minerally or dry. So a lot of people do that. But if you eat your favorite food when you're on this medicine, just like if you were on standard chemotherapy, it is not likely to taste like it did before. And we have really great memories of what awesome foods supposed to taste like. So when it doesn't live up to that, it's hard and it's upsetting and depressing. So if you can trick yourself by trying something you've never tried before, it's possible that you'll think it tastes good because your mind has no memory of what it's supposed to taste like. So just something little you can give a try. Anemia and neutropenia, we may need to hold your medicine. That means like a low hemoglobin or low white blood cell count. We may need to hold medicine or reduce the dose or give blood if absolutely necessary. Liver toxicities are fairly common in the TKI drugs and if they happen, you'll see potentially an elevation in your liver enzymes is what we call them. It's AST and ALT on your printout and then sometimes the bilirubin as well. So we would hold the drug if it were at a high level and wait for your liver functions to come back down and then we'll attempt to re-challenge. Sometimes if you have like a quick, crazy reaction to the drug, like your bilirubin goes really high, your AST and ALT are super high, it is unlikely that we would re-challenge you at a lower dose because it's likely that you will respond the same way. Just because it happens with one TKI though does not mean it's gonna happen with another one so it's still safe to try other things in the future but when it goes really berserker, you don't wanna go back to that medicine. You can have risk for a prolonged QT interval and decreasing the ejection fraction and sous-tent. We usually like to have a baseline EKG and ECHO and then if we need to throughout, I will tell you that on the clinical trials, most of the people who had a drop in their ejection fraction was a subclinical thing, we had no idea. They weren't showing any signs of it and once they stopped it did resolve. In actual practice, I don't see it as much but again, I don't think we look for it as much as we did when we were on clinical trials. So immunotherapy side effects, I think somebody did probably a big old talk on immunotherapy earlier before I got here but what is approved or about to be approved right now are PD-1 inhibitors and CTLA-4 agents, Nevolobab and Ibalumimab are the medicines. Basically all side effects that you get from this medicine are related to the immune response. So what we're trying to do is rev up your immune system so it can find the cancer that's been hiding. So we kind of take away the ability of the cancer to hide and rev up the immune system at the same time. Well that works out great until the immune system goes berserker. So I always say that these drugs are great, really well tolerated until they're not and we don't know when that's gonna be necessarily. It could happen at any point in time. Some people after one dose have a really big reaction. I had one man who was on it for two and a half years on Nevolobab and his only side effect was a runny nose. So and he still hasn't had a side effect other than that at this point. So again everything is fine until it's not and when it's not you're gonna see things like severe diarrhea which is an inflammation of the colon or a really bad rash or your liver function tests get really high because it's attacking the liver. You can get diabetes type one because it's attacking the pancreas. You can have adrenal issues, adrenal insufficiency because it attacks the adrenal glands, inflammation of the lungs, et cetera, et cetera, et cetera. So what I have found is if people have an area of inflammation that already happens, like let's say that they have a little arthritis, sometimes those patients are more likely to have more joint pain while they're on these medicines and that is typically the place where the immune system goes a little bit more berserker in the beginning. If somebody has a history of rash or skin issues, I often see more skin issues with those people. So you can have a little bit of an idea if they already have some autoimmune thing what could happen but really anything could happen at any time and the most important thing for you to know if you're on these medicines is if something happens you can't ignore it. The diarrhea will not go away. If you take a Lomodium and Lomodol it's not gonna cure everything because that's what we tell you to do on the other medicines, right? But that's not what we want you to do on this. What we want you to do is give us a call and we'll help you make the decision but we're likely gonna have you go to the emergency room that's closest to you if at all possible. Now sometimes I realize that that's dangerous because the community places can get a little interesting. So I understand if you would rather come on to us but we wanna make sure we're getting you treated as quickly as possible. And that treatment is going to be with steroids. So the recommendation is one milligram per kilogram. So that means one milligram of typically prednisone per kilogram of body weight at a minimum a day and they're gonna probably give that to IV in the treatment or in the emergency room and then switch you over to a taper orally. If that doesn't work, which it doesn't sometimes there are other medicines that we may move on to while you're in the hospital. So Cytoxin is one of them. There's another drug that I can't remember right now because I don't do my patient. But there are medicines that we may have to move on to. It's important to be in a place that knows what they're doing though if you're getting admitted because these drugs are no joke and they can cause you a lot of problems if they're not managed well. But again, they are fine until they're not. So it kind of sneaks up on you and can be a little scary. Most of the drug companies also have pocket cards that you can take to give to the emergency room physician to say this is what I'm taking and they said I need steroids. If you have any problems with them, have them page your primary doctor, your primary oncologist and they can have conversations about what needs to happen and how things should be handled. But those are kind of the biggies. For that, any questions from me at all? Looks like I finished fast. Good? Okay. Thank you.