 So we're in the end of the home stretch How do I manage the side effects of the treatments that I am taking? Many of you in the audience know Nancy Moldauer who's the nursing director of the kidney cancer program and has been such at UCLA City of Hope and here at Cedar Sinai Nancy Thank You Dr. Ficklin for it was Dr. Ficklin mentioned earlier today Today's program was a series of questions that we feel we wanted our patients to have answers to But the number one question that I'm always asked is how long have I been working with Dr. Ficklin? So just to set everybody straight. It will be 29 years in March Who's counting? So I know you know all the names of these drugs we they were talked about at several time points today and As I know many of you are receiving these medications But what I really wanted to focus on was how we can best prepare you before you start embarking on the treatment So I have about 15 questions. It's gonna go fast and I wanted to throw them out there And as you always do, please let me know what questions I have forgotten that are important to you So I'll start with why is this drug being recommended for me? I think it's important that you know that and that's the number one question As to why your physician is recommending a particular drug and again I think what you've heard today so much evidence as to why one drug over the other what's first line what's second line Which leads us to the second bullet point. What evidence supports the use of this drug? Why am I be why is this drug being recommended for the first time that I'm receiving a targeted therapy? And then of course should I be considered for a clinical trial if yet if yes Which one would you recommend and if not please tell me the reasons why are there any treatment guidelines? Associated with the medication you really need to know what medications you can take with the targeted therapy Which ones are contra indicated? How do these medications work is this chemotherapy? Everyone in the audience today I know knows that this is not chemotherapy, but I can't say that it's true for the rest of the patients that I take care of This is not chemotherapy. It's very different and the mechanism of action is very different Is there a role for combined for combining treatments? We don't get asked that all that often But in the past we used to because in the past we were combining a lot of these agents together But what we found is that there's they're much more toxic when we put Two targeted therapies together and what are the pros and cons of an oral drug versus a drug that's given intravenously? What are the side effects? What can I do to improve them? How long will I be taking this medication? How will I know if it's been successful? Will I be able to travel should I continue working? How will this affect the quality of my life? What financial resources are available to me? Is there any special diet? I should be on can I continue to exercise? How often will I need to see my doctor? When and who do I call if I have a problem? So one of the key items to discuss and I think it's important that you understand what angiogenesis is because it will help You understand the mechanism behind the treatment that you're getting You need to discuss with your health care team a follow-up schedule Just because we give a prescription and we expect everything, you know to like it within a day or two You're going to get your prescription. It doesn't happen that way in our practice We put patients on a very rigid schedule for the first month of treatment and we follow them very closely with monthly treatments monthly follow-up visits You need to share with your physician the past medical history What current medications you're taking and if you're going to receive any elective procedures? One of the side effects with these agents is that they can cause some problems with bleeding So you want to make sure that you stop your medications if you're going to have an elective surgery But not only are the bleeding problems a concern, but we have to be worried about wound healing So sometimes you have to wait up to 28 days even after surgical procedure before you would restart And who do you again? Who do you call for the side effects and how are they going to be managed? What time do I take this medication again? What foods can I should I avoid and? Keep a medication and a blood pressure diary it really helps when you come to have when you see your physician and you can show them either The blood pressures from the previous week the previous month so they can look at the records and they can actually actually see the numbers So for some people and like myself, you know a picture is very helpful in terms of understanding the mechanism of action and then this simplified slide What I just wanted to show you? There's the tumor cell in the center and we know that tumors can Secret factors that actually promote the growth of blood vessels and you can see the the blood vessels kind of opening up towards the tumor and That's exactly what we tried to prevent by giving you these medications that block the growth of blood vessels to the tumor and In the second picture You can see in the red Boxes Here's temporary limus everlimus by the CIVAMED synitinib seraphinib exitinib and fizzopenib and This is a blood vessel This is a tumor cell and you can see where these medications They block all these internal Pathways that lead to cell growth and also the formation of new blood vessels So this is what these drugs do they actually you know They're putting the brakes and as Dr. Figlin often often says it's like putting a block on the dam So that all these internal Growth pathways that the cell knows what to do doesn't get get the signal so the tumor doesn't get the nutrients and doesn't grow it's a bit Challenging and at the same time frustrating in terms of managing the side effects associated with these medications we've been prescribing them for a decade now and I can't say that we better understand the mechanism of action of why You get these particular side effects We have some idea, but it's not a very good explanation as to why they occur So I can lump in the in this column the VEGF Medications that will cause a certain Collection of side effects we talked about the skin changes and well I'll go into that in greater depth increases in blood pressure Fatigue Stornness of the mouth change in bowel habits some laboratory and urine changes loss of hair color Definitely change in appetite and taste and some bleeding and it doesn't necessarily matter if you're on suit tent or Votrient in terms of developing hand foot the way in which we treat it is the same But if you're receiving an mTOR inhibitor on this side Frequently when patients go from The VEGF class to an mTOR It's a much easier transition in terms of the side effects, but I wanted to point out two side effects that The pneumonitis and although rare is something that you need to know about if you're on an mTOR inhibitor and Simply I can describe it as inflammation of the lung tissue and Although rare when it occurs it needs to be promptly recognized and treated and if you develop a cough a fever Some shortness of breath you need to bring this to the attention of your physician right away and The other unique side effect associated with the mTOR inhibitors is that you're going to see some changes in your blood Chemistries elevated glucose lipids and triglycerides again The this class of medication tends to be a little bit better tolerated than the VEGF inhibitors But I just wanted again to point out these two a little bit different class side effects that You do need to know about so we can talk about hypertension and it pretty much is anticipated with all of the TKI's Taking a baseline blood pressure is very important Frequently we initiate or adjust antihypertensive medication We can we would try to monitor blood pressure not always needing to interrupt the dosing of the TKI and if you Bring these if you have a good working relationship with your physician and your team who's taking care of you You don't necessarily have to interrupt the medications because you're prepared to do some dose adjustments of your Routine antihypertensive medications This rarely occurs with the mTOR inhibitors and although we usually see it within the first four weeks of therapy It definitely can happen sooner Which is why we start the medication the blood pressure diaries on the first day of treatment And also as mentioned earlier that hypertension is a biomarker of efficacy in kidney cancer So if your blood pressure increases it may mean that it's working We like to maintain the blood pressure less than 140 over 90 and Again, as I mentioned you you're going to monitor very closely during the initial weeks of therapy There's no specific recommendations as to what antihypertensive to use and also to anticipate blood pressure changes if your dose of the medication is modified or if there's an interruption in in your treatment and there's some Really easy blood pressure of cuffs on the market today This is one that you can wear around your wrist and it does do a very accurate of blood pressure measurement and Perhaps one of the mechanisms that we know about why these medications cause hypertension And that would be the effect actually on the arterial walls And it doesn't allow them to dilate as well when you're taking the TKI and the blood pressures What we're measuring is just the force applied to these vessels at every time the heart contracts So we know a little bit about why this occurs But more importantly, it's the management of it that is number one so fatigue is a universal symptom with these targeted therapies and And we have treated so many patients through the years and Have tried to guide patients as they go through this is that the first couple months or the first couple cycles of this medication will probably be the most intense and Although it's very difficult to kind of accept that when you're starting these medications they actually it actually does get better over time and We have patients now who? Beyond years taking these but generally after the fourth and fifth cycle They're beginning to feel that the side effects have subsided They're getting back to their baseline and they're kind of you know feeling better And their bodies appear to be adjusted to the side effect. So the fatigue indeed will improve The way in which we manage it well, we'd like to screen for other causes if it doesn't go away We don't want people to kind of just lie around all day Develop some type of walking in the morning walking in the afternoon If if a hike or a long walk for 45 minutes tires you out then take a 10 15 minute walk twice a day So you can kind of conserve your energy if you're not sleeping at night. Let your health team know When fatigue Is just so overwhelming we will interrupt the dose and make a dose Modification because our goal is to keep you on this medication and we also want to keep you You know have a good quality of life The next area of side effects are the skin toxicities and these can these are really They range from just a dry itchy skin where there may or may not be a rash to a full-blown rash on the skin Handfoot syndrome hair thinning Generally speaking you will not lose your complete set of hair when you're on these medications But thinning can definitely occur. We see changes in the colors where the because you're going to lose your pigmentation Skelp itching and burning that tends to occur kind of in the beginning of the treatment Inflammation of nail beds and a small incidence of some skin cancers have been noted on patients who have been on the TKIs Here's some pictures obviously Handfoot syndrome and what we notice very frequently is that they seem to appear in the creases of The toes and I'll show you the hands on the next slide and these are incredibly painful They seem to occur in the pressure areas like these could be areas of tight-fitting shoes But also you have to be aware that you know it can occur in areas that you may not expect it So it's very important to carefully examine one's feet and Here's pictures of some hands that had developed some hand foot again in the creases very painful and here's a large area of Calcification well it looks like if the skin becomes very Hard and looks like a blister, but there's actually no fluid underneath the skin What's important is to recognize the early signs of a hand foot syndrome. It can be redness pain tingling and It typically can occur as soon as two weeks into the treatment Up to maybe six weeks or into the maybe the you know sometimes a third cycle. I Think we're doing a much better job at managing the side effects only because we are much more proactive and working with our our patients in terms of starting the use of Moisturizers early on and the thicker the moisturizer the better Informing you to avoid streams of temperature pressure friction to the hands and feet and whenever possible use we're really good shoes and The insoles or gel inserts do help with the hand foot other like common sense things if you if you develop Hand foot on your hands avoid wearing rings. We don't want the rings to get caught Avoid wearing tight fitting shoes use gloves if you're going to do housework gardening work You know, it's difficult to limit the amount of exercise that you like to do and the amount of walking But if your feet are beginning to get painful and if you continue to kind of pound the cement or the surface You're going to have an intensification of the hand foot pay attention to signs of infection and always use some block and avoid direct sun exposure and If all these preventative measures that we talked about are not successful then we do have to have a treatment Interruption and sometimes modify the dose I'm happy to provide this as a handout to you. These are all Different type of products that we use to treat this Recently I have we've been using some prescription Ointments that one is called urea cream the other is cobetasol and they seem to have some a little bit more effectiveness in treating some of the very tough Calisteria's on the hands and feet but again a lot of this is our experience and it's anecdotal We don't have any very good research studies to tell you What? Moisturizer is the best so it's a lot of trial and error and here these are all the products that they're over the counter They're not expensive and very helpful in treating this side effect so moving on Lot of patients will complain of or develop some GI side effects associated with these medications the mouth sores Kind of a burning sensation in the mouth heartburn Taste changes decrease in appetite does the vomiting actually minimal It's rare that we ever have to actively treat nausea and vomiting with any type of prescription medications But there's diarrhea constipation although rare can occur and Then some bleeding from the ball again rare. So if you just think of your entire GI tract being Effective by the TKI's You can see how these side effects kind of set in We make recommendations for how to modify your diet I think you're going to be the best person as to know what foods work and what foods will not We recommend always before starting these medications to having over-the-counter Amodium at the house and we give very specific instructions as to how to use it and Also the use of an antacid because there is some heartburn associated with these medications and if we can you can take some over-the-counter And acid that definitely does help and to alleviate that while you're on the treatment and here's just some of the over-the-counter medications that you can you should have at home and In terms of the diarrhea we talked about the Amodium which is easy for you to obtain, but if that is not effective Then we can prescribe some prescription medicine, but the most important thing is that you need to Contact your health care team when these symptoms occur We don't like to hear that these symptoms have been occurring and we don't know about it It's very easy to become dehydrated and It's easy to do this when you're having you know eight to ten episodes of watery diarrhea a day The other area that's very important also related to the GI tract is really the condition of of your mouth and It's becoming more and more frequent that before you actually start these medications that you visit your dentist and and have a Dental hygienist cleaning of your teeth because again We don't like to have to find things out once you're on these medications that you need to have a tooth extracted or you have a gum infection Simple things like avoiding alcohol mouthwash. We can prescribe some Mouthwashers have a little bit of anesthetics to it probably the best Measure is just warm water rinses up to six to eight times a day if you're able to do that Sometimes we have to change to a children's toothpaste that is not as minty or as spicy And there are some prescription things that we can also recommend when the stomatitis just gets so intense that you can't You know, it really affects your eating again. Here's some again over-the-counter easy interventions that you should have at your disposal while you're on these medications so that you can be very proactive in preventing them and Again, this is one side effect that over time will definitely improve the major medicine the major food that should be avoided on most of these medications is grapefruit and The reason is that it can actually affect the the level of the tki Making it a little bit the level a little bit higher and the incidence of side effects greater and Looking at the top section the snitinib everlimus exitinib those could be taken with or without food. It doesn't matter Snitinib generally is taken four weeks on followed by two weeks of rest Everlimus is daily dosing and exitinib is a medication that's actually taken twice a day or every 12 hours When you're dosing with seraphimib or pizopinib, it's a little bit trickier It should be taken one hour before or two hours after a meal. So if you're on other medications You have to kind of fit in when you're going to take this medication in relationship to when your meal is going to be Seraphimib is given taken twice a day and pizopinib once daily Tems serolimus is given as an IV infusion every week and the combination of bevacivin that it interferon The bevacivin is given IV every two weeks. Where's the interferon as a subq injection? some specific side effects associated with the mTOR inhibitors and And the first one really deals with tems serolimus and that's the medication that's given intravenously and the thing that you Would want to know about and and the nurses who would be administering this medication to you would be the possibility of allergic Reaction during its infusion and that could be manifested by feeling short of breath having some back pain and these are things that a Nurse would be watching you very carefully and observing you during your first infusion with this medicine Also lab abnormalities. I mentioned the increased blood sugar cholesterol and entry increase in triglycerides These are blood tests that should be monitored about once a month And if you can do it at fasting that that's even better And also as I mentioned to always report the nuance of a cough shortness of breath or a fever because we would want to rule out any type of inflammation To the lung so as always We're trying to improve upon the medications that we have to treat kidney cancer and with that always looking at medications that might have a Side-effect profile that's a little bit better tolerated and at the same time having greater tumor control We're looking for a prolonged progression for your survival for those patients who are on these medications with metastatic disease Continuing to have tailored treatment options for our patients and as you heard earlier today the newer treatments being studied the checkpoint inhibitors or the PD-1 and the vaccines and Maybe in the next year or the year after when these newer medications are approved I'll be able to have some intervention some nursing interventions for how to take care of The side effects associated with these medications as well Any questions time for a few questions by for Nancy You can see that her experience is extraordinary