Cachexia and Anorexia in Serious Illness: A Podcast with Eduardo Bruera

Eric 00:09

Welcome to the GeriPal podcast. This is Eric Widera.

Alex 00:12

This is Alex Smith.

Eric 00:14

And Alex, this one’s been a long time in the making. Who do we have with us today?

Alex 00:20

Today we’re delighted and honored to welcome Eduardo Bruera, who is one of the biggest symptom management gurus, if not the biggest symptom management guru in palliative medicine. He’s a palliative care doc and oncologist. He’s chair of the department of Palliative Rehabilitation and Integrative Medicine at MD Anderson Cancer center. Among many other things, Eduardo created the Edmonton Symptom Assessment Scale, or ESAs, which is probably the most widely used symptom assessment scale in palliative medicine. Eduardo, welcome to the GeriPal podcast.

Eduardo 00:57

Thanks. I’m so happy to be here. It’s a great opportunity.

Eric 01:00

I am super excited because I got to tell you, pretty much every time I do a symptom talk to our fellows or our med students, inevitably I include one of your randomized control studies on this from like iv hydration, from delirium to the topic we’ll be talking about is cachexia, kind of how we think about that, the meds that we use to trials around delirium and, you know, antipsychotics and benzos. So super excited. But before we jump into the topic at hand, we always have a song request. Do you have a song request for Alex, Eduardo?

Eduardo 01:40

Of course. CCR. CCR is from my time, and although they were born in your state, they sang about my part of the nation. So I would love to hear something.

Eric 01:53

From CCR and your parts, Texas.

Eduardo 01:56

Absolutely.

Alex 01:57

That’s right. So this song we’re going to do is Midnight Special, which is from 1969. And I like this one because the introductory verse mentions food, and the second verse we’ll do at the end mentions Houston, which is where the NBA Anderson cancer Center is. So I thought this was a nice fit. So here’s a little bit of the verse in the chorus.

Alex 02:20

(singing) “Well, you wake up in the morning you hear the church bell ring and they march you to the table to see the same old thing ain’t no food upon the table ain’t no pork up in the pan but you better not complain boy, you get in trouble with a man let the midnight special shine a light on me. Midnight special shine a light on me or let the midnight special shine a light on me let the midnight special shine another loving light on me.”

Eric 03:30

That was great, Alex.

Alex 03:31

That was fun. Love CCR. Thank you. Thank you, Eduardo.

Eric 03:35

We’ll do a little bit more of that at the end.

Eduardo 03:38

All I can say is that the reason why I’m here is because I was a failed professional bass player. I did try CCR, but guess what? It wasn’t coming out like that. Now, please be aware that this song is sung about a guy who’s in jail. I’m not in jail. I’m an MP Anderson, and the food is probably as bad, but…

Eduardo 04:05

it’s a perfect choice.

Eric 04:07

Well, I want to get on the topic of cachexia, but before we do, Eduardo, I’ve got to ask, since you have been such a leader in our field in palliative care, you know, I love kind of looking at the history of how people kind of went into the field and got interested in this. And you were one of the pioneers in palliative care, created one of the very first palliative care programs way back in 1984 in Canada. How did that happen in 1984? Because I’m guessing there wasn’t a lot of palliative care going on back then, right?

Eduardo 04:42

There was no specialty. There were almost no programs. And basically I trained as an oncologist and I was shocked by the fact that we were focused on the biomedical aspect and we were not even wanting to look at the person’s suffering experience. And so I got shocked by seeing that we had so few resources and so few scales and we were normalizing pain. And somebody said, I hurt a lot, doctor. Oh, that’s normal because you have metastasis to the bone. But the patient would say, well, but it still hurts, though. And then we had people who were losing a huge amount of weight and getting very sad and so on, we had no language.

So I decided that that’s really what I wanted, to focus on the person rather than the cancer. And there were no chances to do that where I trained. So I wrote letters of re Internet area and I got a great guy who was the director of the cancer center in Edmonton, Neil McDonald, who replied and said, you know what? I think this would be nice. Come down here. Let’s see what we can do. I’m the director of a Kansas center, but I am, I’m interested in this. So he brought me, he, he saved my life, in a sense, because the environment was very negative in cancer centers towards anything related to person suffering. But he was the director of that small cancer center. He got my back.

So when people went asking him for more x ray machines or more beds. He said, yeah, I see you need that and we’ll try to find that out. But treated warden knives and that was what kept me being able to go for years. Then he moved on and then finally retired. But he paved the way towards me being able to do this type of work for many years. And so I’m always grateful to the initial times and also the people I came across for so many years. Like both of you who do such a wonderful contribution to all of us by raising our morale when we’re working in an environment where we’re never very sexy. We need this type of push to make us feel that we are part of a community and we are part of a movement and things are changing because we are around.

Eric 06:54

Well, I got to ask you this, because we also need a lot more of what you’re very well known for as a trialist in palliative care, creating both assessments and thinking about how we actually manage certain diseases. Alex brought up the ESAs, the Edmonton symptom assessment scale. Was that developed at this cancer center that you were mentioning in Canada?

Eduardo 07:17

Well, we had a palliative care unit in another hospital that was 510 minutes away. And basically I saw that we had nothing to assess how the patients were feeling. So it was concocted in one of the nursing stations with a piece of paper and pencil. And we said, what are our patients suffering from as persons? Not because of their esophagus or because of their lung or because of their ovarian as persons. And we came up with those ten dimensions that needed limited change after. And it became very popular because it can be done in 1 minute. It’s very simple. It’s translated into 50 languages.

And the most important thing is it has no copyright. Nobody makes a cent out of this. I developed other things over the years, but I made my point that I get very well paid as a salary. I don’t get pharma money, I don’t get tool money, I don’t get copyright of anything. And basically I made it a point that this is for patients and this is for clinicians. And so whenever you see anything that we develop, you’ll see that you’ll always be able to use it without ever having to pay anything, because our goal is to do that. And the truth is we don’t want, I don’t want any patient or family to perceive that when Brera goes to see me, there’s a second interest, a second gain. Or when Brera talks in a congress and says, oh, use this, use that. There’s something. There is no hidden agenda. I don’t get any money from pharma, from copyrights, from anything. And basically, that’s why I think you can do whatever you want with it and change it in any way you want. And I will be always very happy.

Alex 09:00

That’s great. We hope that the creators of the mini mental status exam are listening. You who sold it to a company and now are charging people to use it, this is a much better approach. Thank you for that gift to our community and to the patients.

Eduardo 09:16

I’m glad you bring that up, Alex, because I used it in 100 papers. The mini mental was the beginning of our work. And then one day I got a letter from a lawyer saying I had to pay $1 each time I used it. Shocked. And so we did a public burning of that garbage that, by the way, it was not really developed. Posting, put together things that others had done. And then we went to Bill Breitbart’s Emdas and we never looked back because Bill had the same philosophy. He made the mdas available to anybody who wanted use it, no copyright. And so I’d like to tell everybody who’s listening or watching that there are multiple good ethical tools and you don’t need to pay for them. If they’re asking you to pay for them, burn them. Go Google and you will find free tools that are as good.

Eric 10:07

Well, let’s go to the topic, because one of the questions in Esaas is anorexia and anorexia. And when I think about some of the pivotal studies, your name always comes up here. So I’m going to take it from the very, very top, because I think I know what anorexia is. Cachexia is one of those that kind of always confuses me. Like, how would I define it? How should I define cachexia and anorexia when I’m talking to fellow students or thinking about it in my own clinical practice?

Eduardo 10:42

Sure, Eric. I think the very simple, practical thing is involuntary weight loss. When my patient is losing weight and doesn’t want to lose weight, the patient is having cachexia. And I would never use BMI because when I started working in this field, the BMI was about five or six points lower than it is now. We have an epidemic of BMI and therefore never use the way the patient looks like to diagnose cachexia. And a patient might be looking very chubby, but lost 1015 pounds. That patient past cache. And occasionally I get people calling me and saying, you know, I see a patient who is very chubby. But their albumin is too. Would they have a nephropathy or anything? No, that patient is dying of cachexia. It’s just that they look like a big bmI, but they lost 15, 2030 pounds. They’re not able to synthesize protein, and the albumin is a marker of that. So cachexia, I would put it involuntary weight loss is the number one way to diagnose it.

Eric 11:50

And how important is it? Is that lean body weight or the muscle weight, the sarcopenia that we see? Like, how do you think about that? Is it just loss of. I guess weight is hard because you can actually have a lot of fat weight, but actually lose that lean body weight?

Eduardo 12:09

Yeah, I would say the following. When you lose weight and then you have access to a CT scan in the l three area that shows you the amount of lean body mass that you lost, or even a test like functional, like hand grip. And the patient is really, really low in that that tells you that there is both function and structurally sarcopenia, and that is worse. So weight loss with sarcopenia is worse than weight loss with no sarcopenia. And sometimes sarcopenia happens with minimal weight loss because you’re losing primarily muscle mass.

So while losing muscle is what makes it a deadly problem, a killing problem, and it’s not because of muscle, it’s just that because since you are having sarcopenia, sarcopenia is a marker of the fact that you’re not making antibodies hormones, you’re not synthesizing hormones that are necessary to survive. And as a consequence, you will unfortunately have a shorter survival. So weight loss, number one, if you can combine that with some understanding of how that patient is making proteins, even better to fine tune the real risk that is associated with the presence of the sarcopenia.

Eric 13:29

And I guess it’s kind of hard because it’s like overlapping Venn diagrams. So you have cachexia, sarcopenia, frailty also seems like it’s moving in on that area too, at least like hand grip strength. And the sarcopenia that we see with.

Alex 13:43

That, the unintentional weight loss and unintentional.

Eric 13:47

Then there’s this weird concept of failure to thrive, like out there to doesn’t matter that much what we call, or just like we’re seeing, like, the signs of cachexia, we’re seeing the signs of weight loss and that we should do an assessment and think about how we’re going to manage it.

Eduardo 14:04

I think you’re absolutely right. The Venn concept is wonderful. And I think it’s, you have body composition variables such as weight loss and hypoglyminemia, sarcopenia. Then you have body function variables, including hand grip, stand up and walk and six minute walk, and all the functional variables that happen. And finally, you have what I think are the most distressing ones as we get closer to end of life, that are the symptom and body image changes that are the ones that cause severe distress on this patient.

These three have certain level of integration, one with the other. What we do know is that the two ones, the body composition and the body function variables that you are describing under the term cachexia, sarcopenia, frailty, etcetera, really are associated with worse prognosis and with worse survival. And the other component of symptoms and body image are associated with suffering. And so that’s why they become, they become a very legitimate target for us.

Eric 15:17

I think we know the most with cancer, cachexia. I think we don’t know a lot about why it happens. Hand wave. Hand wave, il something. But how should we think about, why do people with cancer in particular, why do they develop cachexia? Is it just the anorexia they’re not taking enough in, or is there more to it?

Eduardo 15:37

I think in cancer and similar to AIDS, and similar to many metabolic diseases, including diseases like COPD, CHF and so on, we do have massive metabolic changes in our body. Some of them are associated with inflammation as a reaction to the presence of the problem. Some are associated with toxic chemicals, tumor byproducts, insufficiency byproducts, and so on. And those get the body to become basically a flu. The patient is having a flu, and as a consequence of that flu, the person is not able to synthesize essential amino acids. It is unable to do lipogenesis and has symptoms that are secondary to it. And anorexia is one of the secondary symptoms.

So the same as when you get a flu, you lose your appetite. You don’t really get the flu because you lost your appetite. It’s a symptom of that massive metabolic disarray. Now, what happens with the loss of appetite is that it is part of the flu. But if as a consequence of that, we stop eating, we add starvation, so there’s an underlying metabolic disarray, the big flu, and we lose our appetite as part of that syndrome rather than causing it. But once you get that, you aggravate that syndrome by adding a component of starvation.

Alex 17:07

I once heard you in Boston, it was think it’s PSEP, the course that.

Eric 17:14

Oh, yeah, that’s when I first met Eduardo, too, was in PSAP with Andy and Susan.

Eduardo 17:20

Andy and Susan. At that time, they put us in that were in that lousy hotel, or the other side where they already took us to the royal Sonesta.

Eric 17:28

The royal Sonesta. I was at the royal.

Eduardo 17:30

That was the fancy part. Several years before, we were across the street in a lousy little place close to the campus. And we complained so much that they finally took us the other side of the river. And that. That was classy. That was.

Alex 17:42

That was a nice, classy hotel. I remember you had an analogy there. This is a long time ago for me, but something about a conveyor belt or an escalator. Does that ring a bell to you? I wonder if you could.

Eduardo 17:55

Yeah, well, I think that’s an important point that helps us to decide what are we going to do in terms of aggressively nourish this patient. And what I try to discuss with my patients and also with colleagues that we have patients, is when the metabolic factor is on strike, then you are, you can bring all the wood you want, but you’re not going to get furniture because the factory is not going to change that into furniture. And what keeps you alive is furniture. And so I can inject all kinds of amino acids and fatty acids and glucose into you, but that’s not going to change things very much, because what is killing you is the fact that you cannot use that material to synthesize the hormones, the antibodies, the cells that are important to you. And so the same thing happens with pushing hood by mouth, by peg, by TPM when the factory is on strike. Our efforts are aimed at trying to open that factory a little bit. Now, there are situations in which the factory is not completely on track. It’s working a little bit. And the main problem is that there’s no supply. I have profound dysphagia. I have a complete bowel obstruction and a very slow growing tumor.

There are situations in which the starvation component takes over. There you can have some profit from bringing some material into that factory to improve a little bit the patient’s well being and body composition. So it has to be quite personalized. But the underlying problem with all these conditions, unfortunately, is that our factory, our metabolic factory, goes on strike. And pushing a lot of material does not really get the success we would love.

Eric 19:41

So this is the hard part with anorexia and cachexia, right? Is that one, you know, that there is a, let’s say if the patient has cancer or severe COPD that, you know, the factory could go on strike or is going on strike. But there could be a lot of other causes for the anorexia from. Maybe they’re just nauseous all the time from a medicine that we’re giving them, maybe that they’re not taking anything in much because they got a big oral abscess, maybe they’re depressed, maybe they have thrush, maybe they’re constipated. How does Eduardo Barrera think about this when he sees somebody with weight loss? What goes through his mind as far as the assessment that you’re going to do to help figure out how much of this is just that the factory is on strike versus, like, some other component?

Eduardo 20:33

That’s wonderful, Eric, because that’s where we really can make a difference. We cannot very successfully open the factory. I mean, we can open the factory. If the patient has a spectacular response to HIV management or the cancer treatment, then the main factors are removed. Unfortunately, in our side of the business, that’s not that common. But what you are identifying are all those causes of what we used to call, and we still call it secondary cachexia, the real reasons why people are not eating or drinking enough to maintain their nutrition.

And as you’re identifying, constipation, gastroparesis, that happens in almost 100% of patients who are malnourished, and that the repulsive, sterner and epic, whenever you want to prescribe red mitochlorial, may tell you that there’s a whole bunch of interactions and there’s going to be an explosion and you’re going to go to jail. But it’s the only drug that really is good at gastric emptying. So you find gastroparesis, you find chronic nausea, you find constipation, you find dysphagia, you find mouth sores, you find people who are unable to prepare their own meals, you find people who are lonely, who are depressed.

Those are wonderful targets. Once you get into those targets, those are actionable targets, and you can really gain quite a few pounds. And also you give the patient some sense of self efficacy by giving them not only the symptoms that are stopping them from eating and drinking, but also the sensation that there are some interventions from the nutritional and supplements and vitamins and so on that they can do that gives them a bit of a sense of control.

Eric 22:16

Yeah. Oh, I love that. Real quick, gastroparesis, metaclopramide. What, ten tidac, what’s your treatment for that?

Eduardo 22:26

Yeah, it’s a very short half life drive. That’s the problem, and it doesn’t last very long. So you have to take it right before the meals and perhaps PRN every 4 hours if there is more nausea or a sensation of fullness and so on. It’s a drug that those us who are old timers we used to use to give an idea before you give a shot, right? Two milligrams per kilo, five times ten milligrams per kilo. So a patient who is, you know, 70 kilos might get easily 700 milligrams of metoclopramide during the first day of cystplating injections with some decadron.

I would say there is sometimes excessive concern about the use of these agents and use them at the dose they need. Recently, olanzapine has come to the rescue in some cases, and that has some effect, not necessarily on gastro chemtry, but a little bit more on appetite and food intake. And so that could be a nice around the clock and the PRN metroclopamide. But I still continue to use both, even though epic advises me that there’s going to be an explosion and I’m going to lose my license and everything else. That’s something to have in mind.

Eric 23:38

Great. So, any other kind of pro tips, Eduardo? Pro tips on thinking about the assessment that you do for people with anorexia and cachexia?

Eduardo 23:49

Yeah, one of the things I try to do is to put it in perspective, how much is this bothering Mister Smith? If Mister Smith is having major existential, spiritual symptom issues, dyspnea, pain, I try to put that in a back burner, address those first, build a report with the patient, and then move on into the weight issues. And so on the other hand, if the patient has horrible body image, fear and concerns, and thinks that the weight loss is synonymous of imminent death, or if the family are distressed, then it becomes a higher priority.

So the first thing I try to understand is where is this in this patient’s agenda? And then the aggressiveness of the management might be dictated by what else do I need to do for this person? If I need to work on mood, on fatigue, on dyspnea, on pain, on constipation, I would work on those first and then see if in the next visit I made some progress in those areas. And now I can move into the discussion about the food and the supplements and so on.

Alex 24:58

I’m so glad you mentioned the family. I would say the social value of food cannot be overstated. And that for our patients, and particularly for family members, perhaps the number one concern I hear from family members is my loved one is not eating. They’re not eating enough.

Eric 25:19

If we can just get them to eat.

Alex 25:21

Yes. And then I’m interested in hearing the words you use to address that social anxiety. Or not just address, but reassure, but also recommend things like smaller meals, etcetera.

Eduardo 25:39

I think that’s wonderful, Alex, because all our social and even religious events have metaphors of food. My daughter’s birthday. I’m going to go tonight for dinner with the rest of the family. So the celebrations are around meals, the gatherings are around meals. And so there is so much that is lost when the person is not eating, when the person cannot eat. And then there’s two components. One of them is the symbolic meaning of the meal as a social gathering, that I plead that they don’t lose it, that they do not look at the plate, that they look at their loved one, and that they respect the willingness of the loved one to only eat three spoonfuls, not to fill out their plate in a way that they feel nausea before.

Anticipatory nausea by seeing their plate, but respect what they like to eat and to maintain the social value. So partially, I try to do a split discussion with that spouse or that family and say, hey, it’s so important that you all get together, that you’ll discuss, that you’ll talk, that you make all these. All the social value, that from one area, from the other area, that is the actual content of the food, that is what is causing the person to die. I use a little bit the spiel of a factory on strike so that they don’t feel that my loved one is dying of starvation. There would be horrible feeling if my loved one was dying of starvation. And then I try to reassure them that this is not a matter of the person starving to death.

It’s a matter of the body not being able to use energy to create the substances. If I catch them before someone else puts the tube on them or puts an iv and starts TPM, much better if the person is already on it. I wait. I wait and nothing will happen. And then after they tried it for a week or ten days and nothing happened, I say, well, you know, nothing is happening, so should we stop harassing your loved one with blood works and iv’s and all that and things? Because really nothing is happening. And then usually they say that that’s fine, we tried. And then we try vitamins, particularly the hydratological ones. Go down quickly. So I try to encourage vitamin supplementation. I try to encourage amino acids. Not so much protein, but amino acids, so they didn’t have to digest them as much and they can immediately be used for some synthesis and then food that packs, ideally, quite a bit of energy into it.

And if I can use pharmacological also, the family usually takes some time to understand things, and I try to back myself up with some paper, with some label, especially not so much b but my colleagues were younger than me, who might be assistant professors and so on. This is so counterintuitive, right? I mean, I lose my appetite. I’m not eating, losing a lot of weight. And you tell me that food is not the answer. I mean, you really have to have a lot of report and credibility on me to convince me that I should not be pushing this on my loved one. So it’s nice sometimes to back ourselves up with some literature to support them.

Eric 28:56

So I got a question then around how much is like the multivitamin amino acids, how much of that is just giving them something that is very low risk and hopefully low cost with the vitamins versus like a more evidence based approach, because to my knowledge, there isn’t a lot backing up, you know, supplements, vitamins, especially using your analogy, because the factory is on stripe.

Eduardo 29:25

You’re absolutely right, Eric. I think one of the problems is that you do see an occasional quash or you do see an occursion at very, very. You see an occasional massive weight loss that is associated with occasional hypovitaminosis syndrome. I usually won’t measure them. I think it’s very low cost and very low trouble to prescribe them. Usually patients like it because they’re hurting themselves. And so is there just a placebo effect?

I think I’m preventing some potential extra non synthesis that is not happening because you are lacking that bottleneck little hydrosoluble vitamin that might be present. I try to emphasize d if the patient is quite hypogonadic, I try to emphasize testosterone because they are conducive. They might be of some Health. But you are right. Strength of the evidence is not that great. But when you’re losing an awful lot of weight and you’re eating only Oatmeal, I think I have to suspect that the hydrosolubles are a little bit depleted.

Eric 30:29

And the amino acids, are you doing that as a supplement or are you telling the eat Specific Foods for the amino acids?

Eduardo 30:35

I do it usually as a supplement. The problem with specific foods is that, you know, the person has a certain diet for 65 years, and now they have cancer. And now I tell them, you know, we’re in Texas, go eat kale. And then if you don’t eat kale. You can eat arugula and then the patients.

Eric 30:57

And you can only get that in Austin, in Texas, I heard.

Eduardo 31:02

Absolutely. You won’t get any Houston.

Eric 31:05

Everywhere else, they’ll look at you strange.

Eduardo 31:08

So it’s tough for them to have massive modifications at this stage. I’m talking about the later stage. The survivor is a different story. They have to really get on their wagon of improvement. But when the patient has very advanced cancer and they’re not eating and they’re cachectic, I try to emphasize doing the best they can with the diet that they are more likely to adhere to.

Eric 31:30

And where does exercise fit on? I know for fatigue, like cancer related fatigue, exercise is a pretty good intervention. Is there a role when we’re thinking anorexia with exercise?

Eduardo 31:42

We believe there is. We believe there is, and we believe that. I usually never call it exercise because my patients are my age, sixties, mid sixties, late sixties. And if they have not exercised for 30, 40 years, they are not happy. When I tell them, you got cancer, and now on top of that, you have to exercise, they say, well, I haven’t done it. I mean, come on. But what I tell them is, keep yourself physically active. Go for walks, start working, doing on the pool, do house chores. Keep yourself physically as active as possible. If possible, get yourself a little fitbit or a little watch and count your steps, and try to keep yourself physically active.

We do know that this is one of the most effective ways of treating your fatigue. So keep yourself moving. That electricity you make when you walk, it’s very good areas of your brain. And also, if you can spend some time outside with no sunglasses and let that light go through your eye. Forget about the ophthalmologist advice about protecting yourself from macular degeneration. Just go there, get light, because that also becomes electricity that hits very good areas of your brain. So those two can help fight the fatigue. My secondary gain on that is whatever the muscle doesn’t ask, it won’t get. But if the muscle is moving, the muscle will ask, and the little metabolic activity there is will deliver a little bit of energy for that muscle to rebuild. So there is a fatigue advantage, but I think there’s also a sarcopenia advantage.

Eric 33:23

I love that analogy. Okay, I’m going to move on to. We talked about some non pharma interventions, pharmacological interventions. You mentioned olanzapine. You kind of brought that up in the setting of, like, nausea, gastroparesis. Is there a role for olanzapine with cachexia anorexia?

Eduardo 33:44

We think it’s becoming to be a role because it’s a funny drug. It can be quite problematic in people with diabetes and so on. But in reality, our patients have a lot of weight loss and you can kill several birds in one shot. You have a little bit of an effect on insomnia, you have an effect on anxiety, you have an effect on nausea. It’s a powerful anti nausea, especially now it’s been added to chemo, and it’s beginning to be very effective at that. And it increases appetite. In fact, one of the main problems was used for patients with psychiatric conditions was the weight gain.

Patients were gaining so much weight with the Lyme stepping as compared to other atypical neuroleptics. And so there’s something to be said about taking it regularly. Every night, I usually start five minutes at five, five milligrams at night. And that might be a kind of a reasonably well tolerated intervention. If my patient is on any sleeping pill or is in any anti anxiety, it’s a wonderful opportunity to get rid of those and put them on olanzapine at night instead.

Eric 34:53

And how much of that, because we’ll be talking about like megesterol or migase, how much of that is just non lean body weight increases that. You know, what we see when we usually prescribe antipsychotics is it’s not the weight that we want that builds up with these antipsychotics.

Eduardo 35:11

I would say the following. It’s clearly not probably the ideal weight, especially if the person is not moving around and so on. But I usually think that if you change the patients feeling that they are rapidly dying because of weight loss, if you improve a little bit the way they look because theyre not looking as much because theyve got some fat back, that in itself might be a nice, profitable investment. So I would say, yes, youre not going to get what you would love to get.

That is a huge amount of lean body, but you’re going to get something out of it that is. And also, this feeling of anorexia can be extremely distressing. When people have no appetite, they know they’re ill. And so the fact that you have, again, you look at a plate of food with some interest. Yeah, yeah, exactly. That really is good for the morale.

Alex 36:08

Yeah. For the patient and for the family.

Eric 36:11

And since I brought up megestrology, where are we with that? Do you still use that? Is that now out in favor of olanzapine?

Eduardo 36:20

I use megastro because it probably has a different mechanism of action. There’s some appetite, but there’s also genuine weight gain, and there’s a debate about how much of that is lean body, but I think there are some studies suggesting that there is a lean body. If the patient has a clear history of DVT and thrombosis and so on, then I would probably try to stay away from it. But in cancer, we’ve been massively attacked by the immunotherapy cartels, and the immunotherapy cartels have saved a lot of life. I have nothing against that. But many people who are in immunotherapy do not get saved by immunotherapy. Many patients stay on it for too long, and the result of that has been that they’ve taken away the most effective symptomatic agent we’ve ever had. That are corticosteroids. And they help out with fatigue, they help us with anorexia, they help us with nausea. Very good.

Eric 37:13

Adjuvant for pain — magic palliative care bullet right there.

Eduardo 37:18

I always say when I’m on call and they call me and they say, the patient is having this or that, I’m thinking soccer. I’m thinking music, I’m thinking something else. And when the resident stops talking, I say, hey, is this patient on steroids? And when they say, no, I said, that’s it. We can fix it, then we’ll think tomorrow, but we’ll put them on steroids today.

Eric 37:37

Except if they’re on immunotherapy.

Eduardo 37:39

Except when they’re immunotherapy. Screwed my day, because now I have to think about something else. But I think that’s something to have in mind. The fact that this very powerful and effective drug is now unfortunately not available to us brings us to alternatives that we had before, and Megastro comes back as a potential option there.

Eric 38:02

And Megastro is okay because it’s a progesterone, right? It’s not, but it’s okay to use immunotherapy?

Eduardo 38:09

Well, don’t tell oncologist. I mean, so far we got away with it. I hope there’s not going to be some guy doing work there that will take it away from us. But so far, that may be an option. There’s a lot of things that are happening, for example, in breast cancer patients when you put them on the new letrozole. And many of the other agents is a terrible symptom. They are an myalgias, massive osteoporosis, you know, massive sarcopenia. And it makes us wonder, where are we with hormones in general? Males. I am very much into the fact that when you are really hypogonadic, clinically hypogonadic, I try to prescribe testosterone.

Unless there’s a huge contraindication for psalm ones in female patients, I think the initial knee jerk reaction against estrogen is starting to change. And so I would stay quite in touch with the literature and with the primary oncologist to decide, is this patient going to benefit from some hormonal replacement in selected cases? Because the hormonal deprivation is severe. And we need to remember that when we give the patients opioids, opioids cause hypogonadism, not just the cachexia. Opioids are a major cause of hypogonadism, so we need to know that interfering in that area might give our patient some better.

Alex 39:40

Well, I just want to say this is probably the chagrin factor at work, which was like something Alvin Feinstein wrote up a long time ago. You act on your last bed experience. I’ve had so many patients with blood clots on megase megesterol that I stopped using it altogether because I just lost confidence in the drug. And I had so many negative experiences, it made me worried about it. I’m sure there are other listeners out there listening to this podcast who have had similar experiences. Anything you would say to them?

Eduardo 40:16

You know, Alex, we stopped using it for a long time. We had other alternatives. We had corticosteroids, but many times we don’t have them at this point. And I think that what happens with cancer patients die of three things. They die of clotting, they die of infection. Sometimes the subtle infection kills them, and they get hypertensive and they die, or they die of arrhythmias and sudden death. Those are the three reasons why a cancer patient dies. And so there’s no doubt that cachexia aggravates the risk for all those teeth. The patients do not die because of the cachexia. The cachexia increases the risk that those three will happen. There are other reasons, but those are the three main mechanisms.

Eric 41:02

What was the first again?

Eduardo 41:05

They die from clotting, they die from clotting, clotting, thrombosis, venous or arterial clotting. They die of infections, or they die of arrhythmias and death. And those, regrettably, we do not have a good protein infecting or heart resting that we could measure in blood. We only measure tumor math that is very rudimentary to be able to tell us the risk for those events to happen. I hope that in the future we’ll have the ability to detect who are the patients who are at elevated risk for those complications beyond the events that we see.

But one of the things we need to remember is that if I give someone a certain medication and the patient presents with a complication that is expected from the disease, I might create an association between those two. And it’s something that we see a lot with many of the medications we use in cancer. I don’t know if you’re getting called these days, but every other day I’m getting called because somebody has hypotension and they are an opioids, and they say the opiates are causing it. I said, no, they’re not. There’s a dozen reasons why this patient is hypotensive, but please don’t have them be hypotensive and in pain. I’m sure that if you put them in enough agony, their blood pressure is going to go high again because of the agony and the noradrenergic release of the pain. But there has to be another way to bring that blood pressure up. So we sometimes see that those associations, we need to understand that they might happen, but they’re not necessarily causing.

Eric 42:46

And then when you think about anorexia, we’re talking a lot about cachexia, anorexia. Do you ever use, I don’t know where Texas is with cannabis, but maybe Marinol instead, or. We used to see a lot of mirtazapine. I know there’s some, like, mixed evidence now for that. Do you ever use either of those?

Eduardo 43:04

We used mirtazapine, and then the last two randomized control trials were disappointing. I have to tell you that before they become disappointing. We did not find that great response. Occasionally had a great response, but most of the time it was kind of mediocre with regards to cannabis. I worked with cannabis for a number of years with Marinol, with THC and so on. And the truth is, we never found anything very exciting, and so we ended.

Eric 43:29

Up, I gotta say, marinol is more disappointing than Mirtazapine. Four? Yeah, never. And, you know, I know people who, who smoke, who vape it with cancer, and they feel like they get much more than the marital because marital is just THC and there’s a lot of other, it’s probably the cannabinoids. I feel like that are playing a big role.

Eduardo 43:47

You know, we did randomized controlled trials. We didn’t find much. Dorian Strasser, who was my fellow, also did some, and I worked with him on that, and we did not find much. It was disappointing. Regrettably, I don’t think there is that much going on with either CBD or THC at this point. We would love that that be the case, but I normally don’t prescribe it because the other thing I want to remind ourselves is we have published about interaction between CBD and other drugs at the 384 level, and there is a cannabidiol gets eliminated by the three, a four, and another microsomal moieties, and then you might have accumulation of one of the two. And also, when you’re at the pharmacodynamic level, when the patient is on opioids or other drugs, then cannabinoids are not that well tolerated. So we are all waiting for better products. We’re waiting for better ways to get into the endocannabinoid system. That might be more specific, perhaps, but so far we are waiting.

Eric 44:53

I love that. And that kind of gets us into our song because CBD and all this stuff reminds me of CCR. But before we do that, Eduardo, if there’s one thing that you wish our listeners would think about or do when it comes to cachexia anorexia, do you have one main take home point?

Eduardo 45:13

Yes. Acknowledge that is happening. Validate the concern of the patient, and give them some tools. They are not great tools, but give them some tools because that will make them feel validated and that will build rapport. Normalizing the fact that it’s there, normalizing the distress is a great way to go.

Eric 45:36

And I love the idea. I still have that factory image is that that factory may not be on complete strike. So it’s important to think about all of these other factors that we may have a little bit more control over, like managing their nausea, managing their constipation, managing their depression, managing their loneliness. So I just love that analogy. So thank you, Eduardo.

Eduardo 45:58

Thank you.

Eric 45:59

Before we end, Alex, a little bit more, got a little more.

Alex 46:04

Starting with a line about Houston.

Alex 46:07

(singing)

Eric 47:25

Eduardo, thank you for being on the GeriPal podcast. Thank you.

Eduardo 47:29

Thank you for having me.

Eric 47:30

That was wonderful. And thank you to all of our listeners for your continued support.