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Tanovea- The First FDA-Approved Dog Lymphoma Treatment

Tanovea: The First FDA-Approved Dog Lymphoma Treatment | Dr. Douglas Thamm


Summary

Born in a human drug research company, Tanovea (rabacfosadine) is now making history treating lymphoma in dogs.


Episode Notes

Lymphoma in dogs is very responsive to chemotherapy, but it also often relapses. Each time a dog comes out of remission, the cancer often gets harder to beat. Because of this, researchers are constantly looking for new treatments that can either get long-lasting results from the start or be used to beat back the cancer in those difficult cases.

Meet rabacfosadine, known by the brand name Tanovea. This drug is an injectable chemotherapeutic that just became the first ever FDA-approved treatment for lymphoma in dogs. Dr. Douglas Thamm, an oncologist at Colorado State University, has been working with Tanovea through most of its existence, and tells us all about how this drug came to be, how it works, and what we know so far about when it is most useful.

Links Mentioned in Today’s Show:

T-CHOP NAÏVE CANINE LYMPHOMA STUDY at Colorado State

Clinical Trials at University of Wisconsin

Clinical Trials at Oregon State University

Related Links:

Laverdia podcast episode

Lymphoma – What You Need to Know BEFORE You See the Oncologist

About Today’s Guest, Dr. Doug Thamm:

Dr. Thamm is the Barbara Cox Anthony Professor of Oncology and Director of Clinical Research at the Colorado State University Flint Animal Cancer Center. He is also a member of the Developmental Therapeutics Section of the University of Colorado Comprehensive Cancer Center and the Cell and Molecular Biology Graduate Program at Colorado State University. He has authored over 170 peer-reviewed publications and 20 book chapters in veterinary and basic cancer research, is Co-Editor for the most recent edition of the textbook Withrow and MacEwen’s Small Animal Clinical Oncology, and is Co-Editor-In-Chief of the journal Veterinary and Comparative Oncology. His clinical and research interests include novel targeted therapies for animal and human cancer and ways to integrate these therapies with existing treatment.

Other Links:

To join the private Facebook group for readers of Dr. Dressler’s book “The Dog Cancer Survival Guide,” go to https://www.facebook.com/groups/dogcancersupport/

Dog Cancer Answers is a Maui Media production in association with Dog Podcast Network

This episode is sponsored by the best-selling animal health book The Dog Cancer Survival Guide: Full Spectrum Treatments to Optimize Your Dog’s Life Quality and Longevity by Dr. Demian Dressler and Dr. Susan Ettinger. Available everywhere fine books are sold.

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Transcript

[00:00:00] >> Dr. Doug Thamm: So we do know that about 95% of dogs, sooner or later, are gonna get their lymphoma back, even if CHOP worked very, very well the first time. So about 5% of dogs, you treat them once and they go on and die of old age five years later. And we wish it was more than that, but 95% of the time, it’s not.

[00:00:20] >> Announcer: Welcome to Dog Cancer Answers, where we help you help your dog with cancer. Here’s your host, James Jacobson.

[00:00:28] >> James Jacobson: Hello friend. Welcome to Dog Cancer Answers. Lymphoma is one of the most common types of dog cancer, and because of that, researchers have spent a lot of time and energy and money looking for different solutions to treat lymphoma. Recently, the FDA, the Food and Drug Administration here in the United States, has given full approval – not just conditional approval, but full approval – to a drug called Tanovea.

We are joined today by Dr. Doug Thamm. He is from Colorado State and he has been involved in Tanovea since it was just a drug candidate in the human space. And it’s a really interesting journey of how a drug comes to be, and made available, to us dog lovers. Stick around because this is a slightly longer podcast than normal because we get into some of Doug’s backstory, which I think you’ll find fascinating in terms of understanding the people behind the drugs that can benefit our dogs.

Dr. Doug Thamm, thank you so much for being with us today.

[00:01:29] >> Dr. Doug Thamm: Well, thanks a lot for having me.

[00:01:31] >> James Jacobson: So you have been involved with Tanovea for a while, right?

[00:01:36] >> Dr. Doug Thamm: Yeah. Since probably about 2006, in some form or another.

[00:01:40] >> James Jacobson: And what was that early involvement?

[00:01:43] >> Dr. Doug Thamm: That’s a great question. So we started out looking at what now is called Tanovea, it was called something else at the time, as a potential human cancer therapeutic in collaboration with the human drug company that many folks these days have heard of called Gilead Sciences. And Gilead has uh sort of, uh, become a more commonly heard name these days because they’re mostly known for making antiviral drugs, one of which happens to be a COVID medication called Remdesivir. And, uh, again, way back when, mid 2000s or so, they sort of had a drug or a molecule that was very interesting, that sort of came out of some of the work that they were doing with drugs for viruses, that looked like it might actually be a very, very useful cancer drug.

But one of the really interesting and problematic things about this drug for Gilead was that it was a drug that fell apart in blood from rodents. So if you gave it to a mouse or you gave it to a rat, it would just kind of spontaneously disintegrate as soon as it got into the bloodstream. And what that meant is that they really couldn’t figure out how well the drug worked in any of the standard sort of rat or mouse lymphoma models that are commonly used to answer this question before moving into studies with people.

It turned out that the guy who was doing a lot of the, um, sort of animal studies with this drug at Gilead was a guy named Dan Tumas, is a veterinary pathologist. And he said, well, wait, dogs get lymphoma. Why don’t we find somebody who treats dog lymphoma and see if they could try this drug and see how it works and those kinds of things.

And so Dan reached out to me and my colleague, David Vail, who is at University of Wisconsin, and he was here at the time, and said, Uh, Hey, is this something that you’d be interested in? And, and this is kind of what we do, is look at new ways to treat cancer in dogs and cats to help dogs and maybe to help people too. So this was right up our alley and we said, sure, we’d be happy to. And then over the course of the next few years, we ended up treating probably about 70, seven zero, dogs or so with again, what’s now called Tanovea. And we looked at a bunch of different ways to give it: so should we give it once a week? Should we give it every other week?

Should we give it every three weeks? What different doses should we try? Et cetera. But really back then, all of this was trying to figure out A, you know, is there enough here that it’s worth trying in people, and what’s the best way to give it. So how frequently should we give it, et cetera, et cetera. And at the end of this, we all said, yep, here we go. It looks like it works pretty well, um, try it once every three weeks. And so they said, Hey, that’s great. Thanks a lot. They went ahead and started actually some small studies in humans. And then for whatever reason, not too far into it, they basically said, eh, I don’t think we’re gonna keep doing this in people.

And basically put the drug on the shelf. And there it sat for several years until a guy, actually, who is here at Colorado State University named Terry Opgenorth, decided to form a company to specifically look for cancer drugs that didn’t make it in on the human side for whatever reason and see if they could kind of repurpose them into dog drugs. And, you know, when I was talking with Terry about this, obviously one of the first drugs that I thought would be really great to try and bring in would be, again, this drug that’s now Tanovea. Since we had done all this work with it, we knew how to give it, we knew it worked. They knew how to make it.

They’d done all the sort of preliminary testing in normal animals that was necessary, and they were never going to do anything with it. So it seemed like a perfect opportunity for us to sort of take this back and see if we could actually turn it into something that would be useful for treating dogs with cancer.

[00:05:38] >> James Jacobson: Wow. That is a fascinating genesis story. And, uh, we don’t often get to hear the backstory of how a drug comes to market. So that’s really interesting.

[00:05:48] >> Dr. Doug Thamm: Yeah, right?

[00:05:49] >> James Jacobson: It engenders a lot of questions and let me ask those first before we get into Tanovea, and the first one is, wow, you were having promising results in these 70 dogs, why did the human drug company say no, let’s not do this with humans?

[00:06:01] >> Dr. Doug Thamm: So you know that’s the one piece of information that we don’t know the answer to, so.

[00:06:06] >> James Jacobson: It’s bad.

[00:06:07] >> Dr. Doug Thamm: Yeah. When they gave us Tanovea back, they basically said here’s everything we’ve ever done with Tanovea from day one, until it went into the first person, and you guys don’t need to know about that. So that’s the only set of information that we don’t have about this drug.

[00:06:23] >> James Jacobson: Wow. ‘Cause we so often hear, and we talk about on this show, that, you know, if you can do it in dogs, you can do it in people, which is, I guess, what Gilead was hoping for. But we’ll assume only by the silence that it didn’t quite work out that way.

[00:06:37] >> Dr. Doug Thamm: Sure. Yeah. And I mean, there’s a lot of different possibilities. It’s possible they went after the wrong kind of cancer, it’s possible that, uh, the way they were choosing to give it wasn’t the best way to give it, I mean, there’s a million different possibilities, but the honest answer is we, we don’t know. And I don’t automatically assume it was something bad, but for whatever reason, they said, eh. I mean, one of the things that you do need to think about is when you’re dealing with a company that’s this giant, they have so many different things that they can put their money toward that it doesn’t take that much for them to say, all right, I think we’re just going to move on to something different, ’cause there’s ‘so many choices with a big company like that.

[00:07:15] >> James Jacobson: It’s all part of the R & D decision making process and are we an antiviral company or are we a cancer therapeutic company. Okay. So let’s talk about Tanovea for dogs. It’s intended for dogs with lymphoma?

[00:07:28] >> Dr. Doug Thamm: Correct.

[00:07:29] >> James Jacobson: And it was officially approved by the FDA last, uh, last year or sometime.

[00:07:35] >> Dr. Doug Thamm: Yeah, it got full approval sort of in the early fall last year. And it got conditional approval about four and a half years before that.

[00:07:43] >> James Jacobson: Okay. So it’s totally available now. It is available for use by oncology vets or general practice vets?

[00:07:52] >> Dr. Doug Thamm: So technically, it’s not possible to restrict the sale of a drug like this only to somebody with certain letters after their name. So – the drug’s not being aggressively marketed to non-specialists, but if a non-specialist called up and wanted to order it, they could certainly get it. A more practical issue with its use by non-specialists is this is a, what we call an injectable cytotoxic agent. So it needs to be handled in very, very special ways, just like all the other chemotherapy drugs that are used in dogs. And, you know, sadly, most general practitioners are not equipped to handle these kinds of drugs safely.

[00:08:32] >> James Jacobson: Yeah. There’s a lot of protective measures. So it is a chemo agent injectable.

[00:08:36] >> Dr. Doug Thamm: Yeah. It sure is.

[00:08:37] >> James Jacobson: And so, talk a little bit about when it is used. You said it’s used in lymphoma and obviously most people, you know, the standard of care for lymphoma is CHOP protocol. And you said, well, your colleague who’s now at Wisconsin, which is where CHOP – it’s a very small world for a veterinary oncologist, isn’t it?

[00:08:54] >> Dr. Doug Thamm: Yeah.

[00:08:54] >> James Jacobson: So when would you not use CHOP in favor of Tanovea?

[00:08:58] >> Dr. Doug Thamm: Yeah. Great question. So just a slight bit of background. So Tanovea is given as a, as a pretty quick infusion, so a half hour infusion once every three weeks. So not a lot of treatments, it’s not a lot of visits back and forth. So that’s sort of the, what the, what the treatments look like and, generally, if things go well, we plan to do five of those treatments and then stop.

So if you look head to head and compare studies that have been done, looking at a whole bunch of different CHOP based protocols, whether they’re from University of Wisconsin or whether they’re from somewhere else, and compare those to the studies that have been done with Tanovea, CHOP is better. So that’s, that’s very clear.

[00:09:39] >> James Jacobson: Can you quantify that?

[00:09:41] >> Dr. Doug Thamm: Sure. So in previously untreated dogs, we see Tanovea cause at least partial improvement in about 70% of dogs. That number is about 90% with CHOP.

[00:09:50] >> James Jacobson: Okay.

[00:09:51] >> Dr. Doug Thamm: And the average amount of time that improvement lasts with CHOP is in the order of seven to nine months. It’s in the order of four to six months with Tanovea.

[00:09:59] >> James Jacobson: Okay.

[00:10:00] >> Dr. Doug Thamm: So yeah, really just not quite as good. It’s actually quite comparable to if you take just one drug out of the CHOP protocol, the drug called Doxorubicin or Adriamycin, which is also given as a quick injection once every three weeks, but it’s about the same as Doxorubicin as far as how well it works.

[00:10:17] >> James Jacobson: Okay.

[00:10:18] >> Dr. Doug Thamm: So then the question becomes, you know, really under what circumstances would we use it as the first thing to try in a dog with lymphoma? I think I’ll get back to that in a second and say, all right, well, if I don’t use it as the first thing to try, when do I use it? Honestly, the situation in which it seems to be the most useful is as the second thing to try. So we do know that about 95% of dogs sooner or later are gonna get their lymphoma back, even if CHOP worked very, very well the first time.

So, about 5% of dogs, you treat them once and they go on and die of old age five years later. And we wish it was more than that, but 95% of the time, it’s not. And that’s when we’re starting to look for other things that we can try. And really, if you look at the, all the different things that have been looked at, and there’s probably a couple dozen different individual drugs and protocols that have been looked at, really Tanovea looks to be just about the best thing that we know about for that specific situation. So CHOP’s failed, we’re rolling onto something else, there’s a whole library of different things that we could consider. Tanovea seems to be very high on the list based on the number of dogs it works in and how long it works for in that, that what we call the relapsed setting.

So that’s certainly one situation where we think it has a very, very, you know, high likelihood of being beneficial.

[00:11:44] >> James Jacobson: And then the other one, when would you use it primary instead of CHOP?

[00:11:48] >> Dr. Doug Thamm: And then back to the first question. So are there circumstances where we, you would use it as a first-line treatment? Um, yeah.

So this is a little bit sort of contingent on where in the country somebody is practicing or getting treatment, because there’s – we, for example, here in Colorado, draw from a huge, huge, huge geographic area. So we have folks who come from five hours away, one way, to get treatment for their dog with lymphoma, and they might have to do that 16 times if you’re doing a conventional CHOP treatment. Uh, we have other folks who, for one reason or another say, you know, I just can’t take off work 16 times to come up and get treated, you know, with CHOP, is there something that we could do that might still be, be really beneficial, but just doesn’t require the same number of visits?

And there’s a protocol that we’ve looked at that actually includes Tanovea, which is a protocol that alternates it with Doxorubicin. So as I said previously, you know, the Tanovea and Doxorubicin are about the same as far as how well they work, but they work in very different ways. They’re only given once every three weeks.

So what we said was, alright, well, what happens if we give three Tanoveas and three Doxorubicins alternating them just once every three weeks? So it’s a grand total of six visits. It’s not a lot of frequent visits every week or every other week. I wonder what we would get if we did that? And in the initial study that we did looking at that combination, it really looks like those dogs did just about as well as dogs that got CHOP. So pretty, pretty encouraging information. So the average amount of time they did well for was something in the neighborhood of about nine months, which is again, right in that seven to nine month range, which is what we expect to see with CHOP.

So that was super encouraging. There is a confirmatory study that’s, where all the patients have been enrolled and they’re just kind of waiting for the information to roll in to see if basically that those encouraging numbers hold up if we do it again. And so we’re waiting to see about that, but, so that’s the one situation where we do talk about using it sort of in that what we call first line setting. Hey, love my dog, but I just can’t make it in for weekly treatments, you know, what else you got?

[00:14:03] >> James Jacobson: So the advantage of using it, but when you were using it as part of CHOP in replacement of, or going back and forth between Doxorubicin and Tanovea, why would you do that versus stick with Doxorubicin?

[00:14:16] >> Dr. Doug Thamm: Oh, because it looks like if you alternate them, it’s only one extra treatment, but the outcome is considerably better than if you use either individual drug alone.

[00:14:25] >> James Jacobson: Got it.

[00:14:26] >> Dr. Doug Thamm: So that’s the logic there. So I will say there’s one other thing that’s currently being looked at, which is, well, we know that CHOP gets you X. We know that Tanovea gets you Y, what happens if we put them together? So what happens if we stick Tanovea into a CHOP protocol? And that’s actually a study that’s currently ongoing. I think there’s just a couple of dogs nationwide that need to be recruited for that study before we can sit back and kind of just let things, let things cook a little bit and then take a look and see how those dogs did. So that’s a work in progress.

[00:15:01] >> James Jacobson: That’s really interesting. And it also poses an opportunity for listeners if there is someone who has a dog with lymphoma, and if they’re interested in possibly being enrolled in that, that’s something they could do.

[00:15:11] >> Dr. Doug Thamm: Yeah. So if they’re at, uh, near Colorado, if they’re near Wisconsin, and if they’re near Oregon State in Corvallis, I think those are the three sites that are, that are recruiting cases.

[00:15:21] >> James Jacobson: Okay. And we’ll put links to all of those in today’s show notes.

[00:15:25] >> Dr. Doug Thamm: Yeah.

[00:15:25] >> James Jacobson: So, there’s another drug out there that I think is conditionally approved as an alternative to CHOP or, or that sort of is competitive, it’s an oral drug in Laverdia. Talk about the differences between Laverdia and Tanovea.

[00:15:39] >> Dr. Doug Thamm: Sure. So as you mentioned, Laverdia is an oral medication. It doesn’t really fall into the class of drugs that we would call a conventional cytotoxic chemotherapy drug so, this would kind of fall into the class of drugs that would be called a targeted agent. And it really works by an incredibly cool mechanism. So it interferes with the sort of uh movement of different proteins around inside cells.

And to keep it simple, it seems like cancer cells have figured out how to keep certain proteins out of the important center of the cell, the nucleus, that otherwise would kill them. So this little pump that sits on the surface of the nucleus keeps these proteins out. If you poison that pump with this drug, those proteins go into the nucleus of the cancer cell and tell it to stop dividing or to die.

So these, these proteins are called tumor suppressor proteins. And if you can redirect them so they go into the nucleus, which is kind of the brain or the center of the cell, you can actually tell that cell to, to stop dividing or to, or to destruct, which is really, really cool. And it seems like cancer cells have a lot more of this pump than normal cells do, which is where you get this potential advantage or or selective effect on cancer cells.

So super, super cool mechanism of action. This class of drug, a drug very much like this, is actually approved for the treatment of a related blood cancer called multiple myeloma in people. So really, really neat. Um, I guess the other big difference is, and I have to be kind of frank here, Laverdia doesn’t work very well in lymphoma. Again, so if you look at all the Tanovea data put together, it looks like about 70% of dogs or so will benefit from Tanovea. The average duration of that benefit, if you take everybody and put them together, it’s probably in the neighborhood of about 120 days. About 35% of dogs seem to benefit from Laverdia, and the average duration of benefit is about three weeks.

[00:17:39] >> James Jacobson: Okay.

[00:17:39] >> Dr. Doug Thamm: So again, mega cool drug. I honestly think that we need to do a lot more work trying to figure out the best way to use it, so maybe it’s not using it by itself, maybe it’s mixing it up with some other drugs. Maybe it’s using it after chemotherapy to see if we can sort of maintain that remission for a longer period of time rather than trying to use it to treat big tumors. Maybe it’ll actually be better as a drug for some other kind of cancer, not lymphoma. So a lot of work to be done, like I said, super cool drug, really, really looking forward to figuring out the best way to use that drug. But as a single agent in dogs with big lymphoma, despite the fact that that’s kind of what it’s approved for, really the data that’s been published is not, is not that impressive.

[00:18:23] >> James Jacobson: Okay. Let’s talk about Tanovea again, in terms of it being used for things other than lymphoma.

[00:18:31] >> Dr. Doug Thamm: Yeah. So up until very recently, that was not something that we, as oncologists, were allowed to do because of the conditional licensure that the drug was granted by the FDA. So when you have a drug that is conditionally licensed, you are obligated to use it only according to the label. So that’s the disease process that you’re treating, the species that you’re using it in, the dose that you’re giving, how frequently you’re giving that dose. If you use it in a way that is not according to what’s written on the label when it’s only conditionally approved, that’s a violation of federal law.

So yeah, up until recently, we really couldn’t talk about other cancer types where Tanovea might be useful, but now we can, since it’s now has complete or full approval. And again, veterinarians have basically very wide latitude to use fully approved drugs in an off-label fashion. So some of the studies that we’ve done in conditions other than lymphoma include – well, there’s cutaneous lymphoma, which is really just another variety of lymphoma, but it looks like there’s some activity there, but we’ve also actually looked at it in quite a few dogs with various kinds of what are called lymphoid leukemias.

So these are blood cancers that start from cells that are a lot like lymphoma cells, but instead of making the lymph nodes large, these cells actually float around in the blood. So that’s kind of the definition of a leukemia. And then we’ve used it for, again, another cancer type that I mentioned previously called multiple myeloma, which again is another blood cancer that often can affect the bones in dogs.

So, especially in multiple myeloma, this actually looks like a drug that can work quite well. So there’s one study that, that we did quite a while ago, I think it, maybe it was published in 2014, that looked at a small number of dogs, like a dozen or so dogs with multiple myeloma that were treated with Tanovea and almost all of them got better.

There were a couple of dogs who got way, way, way better, and stayed better for years and ended up dying of unrelated causes with no trace of multiple myeloma in their bodies. So yeah, a real potentially interesting tool in our toolbox for multiple myeloma as well. So there are some other oral medications that we know actually can work fairly well for that disease, but in almost every single case, just like lymphoma, eventually they’re gonna stop working.

And then we are looking for other things that we can try. And boy, you know, based on that little small study that we published, I’d certainly put Tanovea high up on the list. We have a followup study that has been done. So about another 20 or so dogs that were treated all over the country with Tanovea with multiple myeloma and we’re kind of working our way through that information so that we can summarize it and get that written up as well. But, you know, after looking at the first half a dozen cases or so, it’s looking about the same as what we saw previously. So I don’t think that was a fluke. I do think this is gonna be a drug that can benefit a lot of dogs with multiple myeloma too.

So some of the questions that we do tend to get are, um, well, what about, there’s 200 other kinds of cancer that dogs get?

[00:21:42] >> James Jacobson: Yes.

[00:21:43] >> Dr. Doug Thamm: What about all those other kinds of cancer, you know, can we use this drug for those? And the answer is it doesn’t look like it, and here’s the reason: so the whole idea behind the way Tanovea was designed was so that we could give a relatively non-toxic, what’s called a pro drug. So kind of like a, yeah, I mean, I don’t know a better word to say, so a pro drug that’s actually given injectably, it floats around, and then it gets turned into a very active and highly toxic molecule only in the cells you want it to do that.

[00:22:16] >> James Jacobson: So this is sort of, you were describing the method of action of Laverdia and how cool it is.

[00:22:20] >> Dr. Doug Thamm: Right.

[00:22:20] >> James Jacobson: So yours for Tanovea is it’s pro, I never heard that term. I like that. So it means it’s sort of-

[00:22:26] >> Dr. Doug Thamm: Right. Yeah. So it’s like a precursor drug.

[00:22:28] >> James Jacobson: Okay. And then it gets activated or actuated when it encounters cancer.

[00:22:33] >> Dr. Doug Thamm: Yeah. But the only cancers that seem to have the little enzymes that are necessary to turn this precursor drug into this highly toxic drug are lymphocytes, which are the white blood cells that turn into lymphoma. So most of the other cells in the body don’t have the machinery that’s necessary to do this conversion, which is-

[00:22:57] >> James Jacobson: So is it an enzyme that is just in these lymphocytes?

[00:23:00] >> Dr. Doug Thamm: Yeah. It’s two different enzymes that are in lymphocytes that most other cells don’t have, which actually make it so that this drug gets into lymphocytes and it gets turned into our cancer killer.

So, because this is really the only kind of cell, and its related cell that makes multiple myeloma that, that tends to have this machinery, these are really the only tumor types where it’s likely to be useful. So we have looked in a Petri dish at some other blood cancers. So we’ve looked at, again, your audience probably knows about other cancers besides lymphoma, so we’ve looked in mast cell tumor cells, we’ve looked in cells from a cancer called histiocytic sarcoma, because these are other blood cancers that we actually see in dogs all the time. And based on what we see in a Petri dish, it does not look like this drug works very effectively in either of those two other cancer types the way it does in lymphomas or leukemias.

[00:23:55] >> James Jacobson: Fascinating. We’re gonna take a break. And when we come back, I want to learn a little bit more about Tanovea, but then I want to actually kind of delve into your backstory and how you got into this stuff.

[00:24:05] >> Dr. Doug Thamm: Sure. Happy to.

[00:24:06] >> James Jacobson: Because I think it’s an interesting one. We’ll be right back.

Welcome back. We are talking about Tanovea. So how much is a course of Tanovea? What, what are the dollars and cents involved in it? How does it compare with CHOP, for example?

[00:24:23] >> Dr. Doug Thamm: Yeah, I mean, that’s going to be a little bit variable depending on each individual clinic and sort of how they choose to, sort of, price all of their cancer drugs.

But this is actually something that, that was looked at a while ago in, you know, kind of a little back of the napkin sort of marketing study that was done. And it seems like a course of Tanovea is about the same cost as a course of CHOP.

[00:24:47] >> James Jacobson: Okay.

[00:24:48] >> Dr. Doug Thamm: So the difference, however, is that with CHOP, the vast majority of the costs are not the drug, they’re the cost of the office visit and the blood tests and the pharmacy fee and the administration fee and the disposal fee and all that kind of stuff.

The drugs are actually dirt cheap. Tanovea is kind of the opposite. So the drug is fairly expensive. But because it’s only given five times, all those ancillary costs are actually considerably less.

[00:25:14] >> James Jacobson: Got it. And what are the side effects of Tanovea?

[00:25:18] >> Dr. Doug Thamm: So some of the side effects are very similar to what we see with a lot of other cancer chemotherapy drugs in dogs, and some of them are a little bit different. So most cancer chemotherapy drugs that we use in common use in veterinary medicine can cause things like a temporary lowering of the white blood cell count, or some temporary intestinal upset, so loss of appetite, mild vomiting, nausea, mild diarrhea, those sorts of things.

So, yep, Tanovea can do those things, just like most of the other drugs we use can in some dogs. I’d say that the likelihood of seeing a lot of issues with the white blood cells is actually low with Tanovea compared to a lot of other drugs. It’s probably average in terms of how likely it is to cause intestinal side effects, but there are some unusual things that we can see. So one of them is some changes in the skin. So, generally not after a single treatment, but after two, three, four treatments, we can actually start to see some thinning of the hair coat. We can see some reddening of some of the skin, especially on the neck and the armpits, in the groin area, and sometimes we can see some ear inflammation as well.

And when we were first sort of working with this agent a long, long, long time ago, and we weren’t really sure what was going on, we saw some pretty rip-roaring dermatitis and some pretty rip-roaring ear changes in some of these dogs. But now that we’ve been using this drug for a good long time, you know, we know what to watch for, we know to kind of make some changes early, even if we see very, very, very subtle changes in the skin or in the ears, we’ll usually, again, do some things a little bit differently to sort of prevent those from getting worse. So we’ll add some symptomatic medications like a little bit of prednisone, or antibiotics, or topical things that you can put in the ears.

And we won’t hesitate, if the dog’s lymphoma is doing well, to sort of give them an extra week off in between treatments, just to kind of, you know, let the skin repair itself a little bit more before we keep going. And again, now that we’re sort of comfortable with how to manage these things, it’s actually very, very rare for us to see, you know, super serious skin or ear changes, changes that are so, so bad that we need to quit. So we’re pretty good at being able to do that and that’s just something that comes with experience.

[00:27:37] >> James Jacobson: Any other side effects? I read something about Westies.

[00:27:39] >> Dr. Doug Thamm: Yeah. So the one other thing that we have seen in a, in a small percentage of patients is what’s called pulmonary fibrosis. So that is a scarring that can occur in the lung tissues.

And the reason that the Westie thing comes up is that this is actually a condition that some Westies are genetically predisposed to, so almost like born with it. That’s not this situation. This is something that really definitely seems to be associated with the drug. There are other drugs that have been reported to cause this as well.

So another lymphoma drug called Bleomycin is known to cause pulmonary fibrosis in dogs and people, radiation, if it’s shined into the lungs, can cause pulmonary fibrosis. So it’s not a hundred percent unique, but this is something that we see in a very small percentage of dogs. So if you look at all the dogs that have been treated with this drug in all the clinical trials that have been done, we’re looking at about 800 dogs or so.

And the number of dogs, or the percentage of dogs, that have had some kind of change in their lungs that could have been pulmonary fibrosis is about 4%. So it’s 1 in 25. And in about half of those cases, it’s been clinically silent. So a little change that they saw on an x-ray or again, if we did a post-mortem examination on a dog aw, they saw a little area of lung scarring.

So 2% it was meaningless, clinically. The other 2% it was actually fatal. So 1 out of 50 dogs had this delayed pulmonary fibrosis. And again, we’re in the process of really trying to sort through all the information that we have about this condition to see if we can figure out what the risk factors are, are certain breeds more likely to get it than others, are pretreated dogs more likely, are, you know, dogs from certain parts of the country more likely to get it than others, like anything we can think of to try and figure out who’s gonna, who’s gonna get it and who’s not. But at this point, what we can say is it doesn’t seem to be dependent on the number of doses that a dog gets. So we’ve seen some dogs who have experienced this problem who have only received three doses.

I know of dogs, who’ve received 15 doses of Tanovea where it’s never happened. So it really kind of falls into this category, based on what we know so far, of what we would call an idiosyncratic adverse effect. So we don’t have any idea who gets it, and who doesn’t, or why it happens. It’s delayed. So the average amount of time it takes before dogs will show up with it after the time they start treatment is about five months. So again, in a dog who is doing great with their treatment, it’s usually after their treatment is complete, you know, a couple months later is when they might start to show problems related to this scarring, again, in this very small percentage of dogs.

So, you know, obviously, as we were going through this whole process, we, we all knew this was a, was a thing, and so did the FDA, right? But at the end of the day, really the FDA said, well, lymphoma is a hundred percent fatal, or 95% fatal, even if it’s treated with the standard of care, here’s something where there’s a 1 in 50 chance of what seems to be a potentially fatal complication. Those seem like pretty favorable odds to us. And I think that was kind of their logic in, as they were sort of looking at this, looking at this drug for approval.

[00:30:51] >> James Jacobson: And then that five month period when, when it can show up is, you know, when you have a dog with lymphoma five months is, you know, to convert to human years, whatever about three years, two or three years.

[00:31:00] >> Dr. Doug Thamm: Oh yeah.

[00:31:01] >> James Jacobson: So.

[00:31:01] >> Dr. Doug Thamm: Right. And that’s a good long time. And again, were it not for the Tanovea, in these dogs that we’ve treated previously, most of those dogs probably would have passed away. So yeah, I mean, I think the – I think this is something that everybody needs to know is a possibility. But I think for an awful lot of dogs, when it’s used correctly, I think the benefits potentially far outweigh the risks.

[00:31:21] >> James Jacobson: Doug, you are so articulate about this. So let me delve into learning a little bit more about you, both you and your wife are cancer survivors.

[00:31:30] >> Dr. Doug Thamm: That’s true. So my wife was treated with surgery for thyroid cancer when she was in college and I’m actually a double cancer survivor. So, um, I was treated for lymphoma, of all things, when I was in vet school actually. And, um, you know, that’s one of the things that kind of made me think about oncology as a career, actually. So I can’t say it’s one of those things where, oh I’m going to dedicate my life to curing cancer for everybody after my experience. But I hadn’t really even sort of thought of oncology as a subspecialty or as a specialty before that.

And I started to learn more about it, and I said, wow, this is really cool. And, and, you know, decided that’s sort of how I wanted to spend my career. And actually about, what, four years ago now, I was diagnosed with a rare, very, very, very low grade kind of leukemia that actually affects the platelets, which are the little cells that float around in your blood and help clot them.

So this is a disease called essential thrombocytemia, so it’s effectively a leukemia of the platelets. And again, it is so low grade that the average survival time after diagnosis is 31 years, which means, um, you know, chances are I’m gonna die from something else.

[00:32:36] >> James Jacobson: In dog years, that’s times seven. That’s, that’s 200 years!

[00:32:40] >> Dr. Doug Thamm: 210 dog years. So, highly likely I’m gonna die from something else, but it is something I have to take medication for and, you know, check in with a hematologist every three months and stuff like that.

[00:32:50] >> James Jacobson: So how did that experience in vet school – it wasn’t one of those Brady bunch episodes where like, I’m now going, I owe this-

[00:32:59] >> Dr. Doug Thamm: Right.

[00:32:59] >> James Jacobson: But what do you think, I mean, without getting too meta, but a little bit, what do you think, to what extent did that influence your decision to go into oncology?

[00:33:08] >> Dr. Doug Thamm: Oh, I think it did a lot. And again, it wasn’t one of those, you know, I’m gonna change my life’s work kind of thing, but, you know, I’ve had a pretty good idea that I wanted to specialize in something, even when I was kind of early in vet school.

I really liked research. You know, I did a fair bit of kind of unrelated research as an undergrad and things like that. So I thought finding a way to incorporate that into my career would be really cool too. And then, like I said, like sort of prior to this, I hadn’t given any thought to the fact that oncology was even a specialty in veterinary medicine.

So again, it wasn’t, it, it was just the kind of thing that made me think, wow, I wonder if oncology is a thing in veterinary medicine, because I didn’t even know. And once I started looking into it, I was like, wow, this, this is really kind of cool. I think this might be a really fun, you know, fun way to, and rewarding way to sort of spend a career.

So I kind of hypothesize that I might’ve gotten there anyway without the whole lymphoma diagnosis, but it might’ve taken me a little bit longer before I thought to take a look at oncology, if you know what I mean.

[00:34:09] >> James Jacobson: I do. Do you think that your own personal experience with cancer in your family has informed the way you talk with clients and patients, dog owners?

[00:34:18] >> Dr. Doug Thamm: That’s an interesting question. So, you know, actually we spend most of our time when we’re talking to clients, dispelling a lot of the myths that clients have about what cancer treatment is gonna be like in their pet and how it’s completely different from how it is in humans, you know, despite the fact that we use the same drugs.

So I guess I would say, no, not really. I don’t, I don’t think I usually sort of put my own personal experience into it too much because the experiences are so different. But, I mean, really interestingly, when it comes not sort of to the nuts and bolts of, you know, what drugs are we gonna give, when, and all those kinds of things.

One of the things that I actually found really surprising is how similar the conversations are that we have with our owners and that human oncologists have with their patients. So the tone, the tenor of the conversation, the kind of points that are hit, et cetera, really are remarkably similar. And that was really surprising to me when I sort of had an opportunity late in my residency to actually spend some time hearing the talks that the human oncologists do. And yeah, I was blown away at, at how similar the talks are.

[00:35:25] >> James Jacobson: When you’ve met with your own oncologist, do you guys like, when they find out, oh, what do you do? I’m a veterinary oncologist. How does that conversation go?

[00:35:33] >> Dr. Doug Thamm: Oh yeah. So it’s really interesting actually. So my hematologist and I are members of the same cancer center. So we’re both members of the University of Colorado Comprehensive Cancer Center. And we’re actually both in the same sub section of that, the developmental therapeutic subsection of the, of the cancer center. So we’re actually colleagues. And he actually will come over and attend some of our meetings and some of our journal clubs. He organizes a meeting every year that I go to. I mean, it’s a really interesting relationship, but when I go in for my quarterly re-checks or whatever they are, we usually spend about five minutes talking about me, and then 10 or 15 minutes talking about, you know, what’s new, how’s your research going? You know, those kinds of things. So it’s a, it’s a very interesting relationship.

[00:36:17] >> James Jacobson: That is fascinating. So you, you mentioned a few moments ago about, you often spend a lot of time with clients talking about the differences and debunking some of the myths. Let’s go over those things, the, a standard conversation where you kind of tease that apart about the difference between human and dog cancer.

[00:36:34] >> Dr. Doug Thamm: Yeah. So, I mean, I think that’s a really critical piece of information for owners to have when they’re sort of trying to educate themselves and make a decision about how they might wanna choose treatment for their pet with cancer. And obviously as a medical oncologist, most of what I talk about is medical therapy.

So here at Colorado State University, actually, we have what’s called an integrated service. So I work shoulder to shoulder with surgical oncologists and radiation oncologists and a very vibrant clinical trials group. So I do feel very comfortable talking about those things as well. But, again, as a medical oncologist, I mostly talk about drug therapy.

And that’s the thing that sort of freaks owners out the most I think, is this concept of what, wait, you’re gonna give my dog chemotherapy? What’s that going to be like, you know, my great aunt Harriet had chemotherapy and she was in and out of the hospital all the time and she lost all her hair and she was miserable and I would never do that to my pet.

So again, a lot of the conversation that we have initially is sort of talking about, well, let’s back up a second. I mean, yes, you’re absolutely right. With a small number of exceptions, and thankfully that number is growing, the drugs that we’re giving to people’s pets are people drugs. They are human cancer drugs.

And so it would be only logical to, to sort of think about some of the side effects that we might have seen friends or family or ourselves have with these drugs. But the way that these drugs are given in veterinary medicine is actually quite different in two very important ways. So one of them is that the doses that we give to dogs and cats are much lower than what even a similarly sized person would get.

And the other big difference is we’re very much into usually giving a single drug at a time, you know, occasionally two, usually, one. Whereas in humans, it’s quite common for them to pour on two, three, four, five drugs all at the same time. And really with those two changes, so reduced doses and fewer drugs given together, we really try to find a dose of medication that is gonna be actually very well tolerated by the majority of our patients. So we can’t ever say that the likelihood of seeing an unpleasant side effect is zero. If it was, the doses that we were giving would be so low they probably wouldn’t do any good. But we really try and make it so that two thirds of dogs and cats have pretty close to nothing in the way of, uh, of a side effect from treatment.

And in the third that does have some kind of side effect, it’s usually something that’s not very bad, goes away in a couple of days at home, you know, just with sort of supportive care. We’ll generally say that the likelihood of a serious side effect, something bad enough to land an animal in the hospital, is about 1 in 20. So one dog out of 20 might just be sort of uniquely sensitive to one particular drug. So if you’ve got a chance, again, let’s look at the lymphoma example, you got a 90% chance of having that lymphoma go away and only a 5% chance of a serious side effect. I think those are pretty favorable odds. And sort of, that’s kind of the statistics that we usually tell owners about, really, to help to, again, allay some of those fears that they might have about, oh, my dog’s just going to be sick all the time and it’s going to be miserable.

I mean, I wouldn’t want to do this for a living if all my patients were miserable all the time. And I think we do a really good job of really minimizing the likelihood of a lot of unpleasantness occurring.

[00:40:01] >> James Jacobson: Now I’ll ask you to polish your crystal ball and look into the future. What do you see? What are you excited about?

[00:40:08] >> Dr. Doug Thamm: So I guess one of the things that’s really sort of almost revolutionized cancer treatment on the human side in the last decade or so is, um, what’s called immunotherapy. So finding different ways to trick the immune system into recognizing cancer as more foreign than it currently does. So obviously all of these cancers in dogs and cats and people have, by necessity, evolved strategies to avoid getting picked off by the immune system. Right? Otherwise they never would have gotten bigger than a speck to begin with because the immune system would have taken care of it. So finding ways to kind of reverse that, so block those, those pathways that these tumor cells have used to basically be ignored by the immune system to try and sort of make them stand out more, has been a really interesting and very powerful means of cancer therapy, again, in the last 10 years or so for certain kinds of human cancer. So melanoma, kidney cancer, or some lung cancers – I mean, there’s a long list. And a lot of these strategies kind of have not quite trickled into veterinary medicine yet.

So most of the drugs that sort of fall into this category, the ones that seem to be the most promising and are the furthest along on the human side, they’re also referred to as immune checkpoint inhibitors. So these drugs, they’re not pills, they’re not small, what are called small molecules. These are actually antibody based therapies.

And one of the big problems is you can’t give these human antibodies to dogs and expect them to work. They’re very, very human specific. And unfortunately what happens if you give an antibody like this to a dog is, the dog recognizes the therapy as foreign and eliminates it.

[00:41:56] >> James Jacobson: Oh. Not exactly the intended-

[00:41:57] >> Dr. Doug Thamm: Which is not what you want, right? So really what’s had to happen is people have had to go back and make dog versions of these drugs. So you can’t just buy the human version and give it, you got to go back to the drawing board and remake it. And that’s actually been a very, very slow and laborious process but, you know, there are rumblings out there that there may be some drugs that fall into this class available in the not too distant future.

And if they work as well in at least some dog cancers as they seem to in some human cancers, that would be a real exciting new tool in our toolbox. So, is it gonna take away the need for uh surgery and radiation and chemo? No, of course it’s not, but again, I think it really is going to potentially find a real interesting place in, uh, sort of our arsenal of different treatments that we can reach for at least for certain kinds of cancer. So that could be very exciting.

[00:42:50] >> James Jacobson: Well, and that is really interesting. So, uh, Dr. Doug Thamm, when that happens, will you come back and share a little bit about that with us?

[00:42:57] >> Dr. Doug Thamm: Yeah, I’d be more than happy to.

[00:43:00] >> James Jacobson: That is awesome. Thank you so much for being with us. I really appreciated it. Thanks so much. We will post connections, ways to get in touch with you in the show notes. But do you want to share something here on the podcast?

[00:43:12] >> Dr. Doug Thamm: Sure. Please check out csuanimalcancercenter.org. So, um, that’s actually the link that will take you directly to all the information about the Flint Animal Cancer Center here at Colorado State University, and there’s actually a wealth of information for owners, for veterinarians, for everyone who’s interested in learning more about animal cancer.

[00:43:32] >> James Jacobson: Dr. Doug Thamm thank you so much.

[00:43:34] >> Dr. Doug Thamm: My pleasure. Good to talk to you.

[00:43:38] >> James Jacobson: And I want to thank you for tuning in and hitting that play button today. I think Dr. Thamm is quite articulate and we will have him back on a future episode of Dog Cancer Answers. We have an entire back catalog of shows, if you haven’t heard any, you should check out our website at DogCancerAnswers.com. And also, if you don’t mind, and you enjoyed today’s show, please tell a friend about Dog Cancer Answers. It can really help a dog lover who is going through the process of treating their dog with cancer.

Well, that is it for today’s show. On behalf of everyone here at Dog Podcast Network, I’m James Jacobson, wishing you and your dog, a very warm Aloha.

[00:44:24] >> Announcer: Thank you for listening to Dog Cancer Answers. If you’d like to connect, please visit our website at DogCancerAnswers.com, or call our Listener Line at (808) 868-3200. And here’s a friendly reminder that you probably already know: this podcast is provided for informational and educational purposes only.

It’s not meant to take the place of the advice you receive from your dog’s veterinarian. Only veterinarians who examine your dog can give you veterinary advice or diagnose your dog’s medical condition. Your reliance on the information you hear on this podcast is solely at your own risk. If your dog has a specific health problem, contact your veterinarian.

Also, please keep in mind that veterinary information can change rapidly, therefore, some information may be out of date. Dog Cancer Answers is a presentation of Maui Media, in association with Dog Podcast Network.


James Standing in Office

James Jacobson

Host, Podcast Veteran

Maui, Hawaii, USA

James is one of the hosts on Dog Cancer Answers and founder of the Dog Podcast Network, a series of shows dedicated to all things dog.