Hello everybody, thank you ever so much for tuning in to the webinar. Today we're talking about the first steps to start giving chemotherapy in practise. My name's Owen Davis.
I work at Bristol Vet Specialists in Bristol and I treat dogs and cats with cancer. These are my disclosures here and you'll see that none of them are relevant for this session. The idea behind this talk is from comments I frequently get like this.
I would like to refer this dog for treatment because we haven't got the facilities for chemotherapy here. And as I said, I, I hear this quite a lot and actually there are no specific facilities for chemotherapy that we need. And I'd like to show you that giving simple chemotherapy treatments in-house is actually much more accessible than you might initially think.
So in this talk we're gonna go through some of the important preparation I think you need to do if you'd like to start treatment with chemotherapy in-house. And it all starts with a diagnosis, so I've got you on now. This is Ted.
Ted's a six year old male neutered Bassett, and he's got the most common type of lymphoma. His owners have brought him in because he's got lumps under his neck and in front of his scapulae the size of oranges. You're examine him and you see massive lymphadenomegaly of the mandibulars, the popliteals, the pre-scaps, the axillary, and the inguinal lymph nodes.
He's otherwise very well and happy. You take cytology from a couple of nodes and it comes back with a high grade lymphoma, you run a par test and it's a B cell case. So this will be the most common type of multicentric lymphoma that you see in practise.
Now Ted's owners are very nice, they're very conscious of the costs, and so you haven't done any staging tests, you've offered referral to a specialist centre, and they've declined. So you're in this situation now, you've got a six year old dog who's lovely and his owners are lovely, and you'd like to do the best for him and do your best for them. What can you do in-house?
So the first step is to decide what treatment is necessary, what do you feel is the best. And you could use books, for example, these or PubMed, and do some research. And my first point then.
Is on choosing the right treatment. One measure of a treatment, that tends to be associated with being the best or overall efficacy is survival time. So if you do some research, you'll find papers like this, treating dogs like Ted's with essentially a CHO protocol, and they're reporting a survival time of 251 days.
And in this paper, very similar, survival time 51 weeks. But this is an important point. Survival time is a very poor measure of an induction protocol.
The survival time depends on many different things, not least other treatment the dog has. In this paper, 31% had rescue therapy, and that's not studied. So the actual effect of the protocol given is measured as the disease-free interval, which was significantly shorter, 204 days or 142 days depending on how well the dog responded.
And in this paper here, again, the median disease-free interval was about 60% of the overall survival time. So my first key point. When you're looking at what protocol is best, please use either disease free interval or progression free survival as a measure of the efficacy of an induction protocol and bear in mind that lots of treatments add up to make the overall survival.
So for Ted, you've done some research and you don't have to look very far to find that there's a clear standard of care treatment in this disease. And this is the CHOP protocol. CHOP is an acronym of cyclophosphamide, doxorubicin, vincristine, and prednisolone, so it's actually CDVP but oncologists just can't spell.
There's a few different permutations of this, and the most common one is the University of Madison, Wisconsin. With this induction protocol, you'll, on average, you'll get the disease into remission for 9 or 10 months. If you're not familiar with the CHOC protocol, it may sound complex, but actually it's quite simple.
It consists of 4 cycles of this week 1 vincristine, week 2 cyclophosphamide, week 3 vincristine, week 4 doxorubicin, and week 5 off. And then you repeat it another 3 times. In the first cycle, you give a tapering course of prednisolone, but usually you don't have to give that in subsequent cycles.
Now, here's the thing, Doxorubicin administration. Is higher stakes than being Christine administration. It's a more expensive drug.
It has to be given as a longer infusion, and there's a risk, risk of extravasating the drug that far exceeds the risk of extravas in vincristine. It can cause an incredibly nasty wound if you extravasate even one molecule of doxorubicin. So understandably if you're starting out to treat chemotherapy in practise, do you want to offer this first line?
So another treatment that you could consider is a much simpler treatment of a cop protocol, and it's pretty much the same thing but without the doxorubicin. There's lots and lots of versions available. The one I use is the Ohio State version, which involves 8 weekly injections of vincristine and giving cyclophosphamide orally at home.
Now if you look in the BSAVA formulary, you'll find other versions which are equally as good. So Once the 8 weeks are over, you can either choose to continue the C, the COP protocol if it's going well and split up the injections to every other week and then every 3rd week, or like I do, you can go with a maintenance therapy. But with this kind of treatment, the median remission is a lot lower.
Remember we said that with a CHO protocol, the median remission would be 9 or 10 months, with COP, it's more like 6 months. So it is very much second best. And the question to briefly consider is, is this OK?
There's a better treatment that is available. Should we be just offering the chop protocol? And I think providing the owner's fully informed and involved in the decision making, I think it's fine.
This touches on a whole issue of contextualised care and there's a lot of chat about that in the veterinary literature and other places at the moment, but I don't think it's anything new. Is that fair to say? I think, you know, generations of good vets have adapted the treatment they give to their patients and the circumstances of their client.
And that's fine. I think if the client understands their options and the implications, there's nothing wrong with giving a less definitive treatment here. So in this case, I would say if, you know, the best treatment will be the CHP protocol, however, that will necessitate referral because I don't feel comfortable giving some of the drugs in-house.
A second best treatment would be the COP protocol, which we could do here, and although the remission isn't as long, it's a cheaper protocol and it involves fewer visits. That's along the lines of discussion that I'd have. Now, In this situation as well, I think it's fine to recommend a treatment.
And when I graduated from vet school, I was of the opinion that I had to educate my client so that they had all the information they needed to make the best decision for them. And that's a very laudable aspiration, but it's also very impractical. Clients.
Frankly, aren't, aren't able to evaluate all the information like we can. If you think of the years of training you've had and the years of postgraduate experience that go into every decision you make, that's why it's easy, that's why it's quick and simple for us to make a decision. If you hand a decision, I can treat you with this or treat you with that to a client, they.
Tend to feel a sense of despair because they know that that they're not really qualified for this as well. So I think we need to make them aware of the treatments, and then we need to make them aware which one we'd recommend. So I might say something like, after listening to what you say about how worried Ted is when he's at the vet's, I'd recommend a treatment with fewer visits.
After recommending how concerned you are about costs and making sure you save money to pay for treatment later on, I'd recommend this cop protocol. Alternately, if the client were saying things like, I want to do the very best for him, I'd want him treated just like you or me would be treated in an NHS hospital, I'd say, well, based on what you're saying, I'd recommend the, the CHO protocol. It's more intense and more expensive, but it is also likely to give the best remission.
An interesting side note here is this little study I did 10 years ago now, where we compared cases of lymphoma just like Ted, where they were induced with a COP protocol and later rescued with a doxorubicin containing protocol. And we compared those to dogs who just had the CHO protocol alone. And if you look at the, the red line, which is the cases you had the CHO protocol, but no rescue.
It is very intimately entangled with the green dotted line, which are those who had cop and later rescued with doxorubicin. So in this study, which was limited by sample number, it didn't seem that giving a cop protocol as induction undermined the overall prognosis, providing you later use the doxorubicin that you initially left out. So we decide then with Ted to go for the 8 week COP protocol as I described.
And we're gonna need to make sure we're OK with the potential adverse effects, and also that Ted's family are too. And when I start discussing chemotherapy, with people, I always make the point that it's much less hard hitting than they, than they might assume. The reason is because most people endure very hard hitting cancer treatments because they're, the average human cancer patient will have decades to fight for.
Very sadly, with the best will in the world, a dog or a cat is never gonna have decades of natural life to fight for, more 3 or 4 years in most cases. So on the one hand, we don't want to make them poorly, because that's not fair. And on the other hand, we don't need to make them poorly with chemotherapy to get an acceptable outcome.
We use very similar treatments to people but much, much, much lower doses and therefore our patients should be happy and healthy for the duration. Let me illustrate that here with the CHO protocol, which is the standard of care for treatment of human B cell lymphoma as it is canine. These are the canine doses and these are the human doses.
You'll see that humans get double the dose of vincristine, 3 times the dose of cyclophosphamide, and 60% more doxorubicin. And in dogs it's spread over 5 weeks and in people. What time interval do you think it's spread over?
One day, all given together, bish bash bosh, OK. So you can see by this example that the kind of treatment we're giving is an order of magnitude less aggressive in dogs than it is in people. But when it comes to discussing the specifics of the side effects.
I tend to say to owners that every anti-cancer drug that I'll ever discuss with you, either now or later, could have 3 things. Could cause alopecia or hair coat changes. Could cause a tummy upset.
Or could suppress the blood cells. Additionally, for some drugs, there are drug specific side effects, and just to avoid overloading you with information, I'm not gonna tell you about every possible eventuality of every drug, I'll introduce, concerning drug specific side effects. Before that drug is used.
So with alopecia, in most cases we don't tend to see it. It's, most dogs and, you know, pretty much all cats, you don't see hair changes. But in the breeds you need to strip, like, the poodles and bichon frise, you can see patchy alopecia like this Labradoodle here.
May look a bit weird, but it's not bothering the dog. Cats, even less so the main thing in cats is that they can lose their whiskers. So if I, my patient is a Border collie or a basset hound, I'm not gonna discuss hair coat side effects very much because they'll either be non-existent or very, very mild.
Gastrointestinal upsets are more important. And I make the point that this can involve hyperrexia, eating less as it can vomiting or diarrhoea. It's also important for us to bear in mind that there's two mechanisms of gastrointestinal toxicity.
You can have the drug flowing through the veins stimulating a chemo chemoreceptor trigger zone, and that causes acute sickness while the drug is being given or just afterwards. Carboplatin's an example of a drug, that does that. You can also have damage to the intestinal epithelium, and that's not gonna be manifest for a few days because you've got those dividing crypt cells have to rise to the top of the villy for the problem to become apparent.
So. With the with the drugs that cause that, and vincristine's a good example, the gastrointestinal upset tends to occur a couple of days later. This is useful to know.
Because it tells us that Vincristine, if we, if we give mopitent or an anti-nausea drug when we give him Vincristine, it's not really needed. If we're giving carboplatin on the other hand, for example, for an osteosarcoma, then an anti-nausea drug can be pivotally important. And taking this further with something like vincristine, if we're worried about gastrointestinal issues, I wouldn't give meopetent now, but I might consider giving it in a few days, along with other treatments like probiotics or binding agents in case there's diarrhoea.
And to come back to Doxorubicin, well I'm afraid Doxorubicin is very good at doing both of these, it can cause acute vomiting and delayed vomiting. The prevalence of GI toxicity or rather the severity is strongly related to the drug, and as a rule of thumb, the oral drugs like cyclophosphamide. Tend to be very light on the gastrointestinal tract, and the coloured drugs like doxorubicin or epirubicin are very heavy, the vincristines in the middle.
In this paper here, they looked at gastrointestinal toxicity after giving vincristine or cyclophosphamide, and they found that they were very mild and principally with vincristine. They also looked at prophylactic administration of moppotent, and that didn't seem to be important, so they concluded only to give Moropotent in particular cases where a dog is particularly sensitive. We're coming on to milo suppression now.
When we talk about chemotherapy induced myelosuppression, we're principally talking about suppression of neutrophils and platelets. That's because they have the fastest turnover time in the bone marrow. Sometimes people send me a haematology in and ask me, is this dog OK to receive chemo, and the only abnormality is an anaemia.
Bear in mind that red cells last 80 to 120 days in dogs and 60 to 80 days in cats. So if the, if you're thinking the chemotherapy you gave last week has made the dog anaemic, well. You're probably wrong.
The dog's anaemic due to something else, quite possibly the cancer. So we very often don't look at the red cells in deciding whether we need to give chemo or not. At the doses we give, most neutropenia, most thrombocytopenia would be subclinical.
We very rarely push dogs or cats down, you know, to the absolute limits, and that's in contrast to human medicine. So most dogs, even if they are a bit myelosuppressed, should have enough neutrophils and enough platelets to carry on with life as normal. But in, at times, antibiosis may be needed.
And at times we'd have to be very careful and restrict activity due to thrombocytopenia, but that, that would be really quite rare. The other thing that's useful when you're giving the cop protocol. Is a couple of peculiarities within pristine and cyclophosphamide.
Vincristine can actually encourage mega carriocytes to break up and so it can raise platelet numbers. And you might be familiar with using vincristine to treat immune mediated thrombocytopenia. Another thing with cyclophosphamide is that megakocyte precursors have lots and lots of an enzyme which can inactivate cyclophosphamide.
So in other words, cyclophosphamide is a platelet sparing drugs and doesn't really have any significant effect on platelets. So in Ted's case with a COP protocol. If he turns up severely thrombocytopenic, I'd be worried about the lymphoma getting into his bone marrow than I would be worried about the effects of the drugs.
And that would mean if I see him extremely thrombocytopenic, I'd be thinking about definitely giving chemo rather than holding off chemo. When you look at the degree of myelosuppression that you get. You'll see that vincristine is very, very light on the bone marrow, one of the good things about the drug, but, these oral drugs like cyclophosphamide and lamatine are much more myelosuppressive, and in this case we've got cyclophosphamide as intermediate.
And then finally we talk about the drug specific side effects that we might see. Now In dogs, vincristine can cause a peripheral neuropathy. And that's manifest as ataxia.
In cats, vincristine can also cause a peripheral neuropathy, but this affects the myenteric plexus in the gut, and it's manifest as constipation. In dogs, we worry that cyclophosphamide can cause sterile hemorrhagic cystitis, and in cats that's not believed to occur. So bear in mind when we're talking dogs and cats, we don't want to extrapolate side effects from one species to another.
What can we do about trying to minimise side effects or prevent them as much as possible? One thing we can do is consider whether our patient could be a carrier of the MDR1 mutation. And this is the mutation that's often called the ivermectin sensitivity mutation in collies.
It could also be called the vincristine sensitivity mutation because this MDR1e-flux pump exports both ivermectin and vincristine and actually many other drugs in the cells. So, this is something that we, that know affects collies, and that's where it's best characterised. But for those of you in the UK, a point to consider is that if you ask a British person, particularly a British vet, to think of a collie, they think of this guy on the left here.
A lot of research on this mutation has taken place in America, and if you ask an American person to think of a collie. They think of this, this dog here. Two very different breeds.
And this is very important when you consider the prevalence of this mutation, particularly in the UK. Border collie is really, really, really low. In this study, 2% of the border collies were carriers of the mutation as heterozygotes, and no border collies were homozygotes.
Look at the rough or the smooth collie, then it rises to 70% or 50%. So this explains why if I have a rough collie, I will test him or her for the MDR one mutation, but if a border collie, I won't. Other breeds to put on your radar would be the Australian Shepherd, where actually the prevalence of this mutation is really pretty high in the UK.
Or the Shetland sheepdog or the old English sheepdog. And if you want to explore this further, you could look on the website of Washington State University. They've got a really useful page for MDR one prevalence in lots and lots of different breeds.
Regardless of the breed though, something you could consider to reduce the adverse effects of chemo is to starve before chemo is given. Starving helps the cells in the body deal with stress, all kinds of all kinds of metabolic and chemical stresses, so it makes them tougher, in other words. And there was one study of women with breast cancer who were in a crossover trial, and they were asked to starve themselves before chemotherapy administration, for a period of time, and then asked to cross over into the other group where they didn't starve before chemo for a period of time.
And they found it was difficult to to finish the study as planned because the ladies had been starving before chemotherapy initially. Had one go at eating before chemotherapy, and then they, they felt so different that they went back to starving again. The effect was really quite marked.
And in this study here, you found nausea in dogs, 53%, if they were fed before chemo, 7% fasted, anorexia, 60% fed, 7% fasted, and lethargy again, 73% fed, 40% fasted. This isn't just a vincristine thing, it also, has been done in dogs with doxorubicin. And the dogs who vomited when fed, 80% experienced no vomiting when fasted.
Now to get this benefit, you do need to starve for, you know, up to 2024 hours before chemotherapy is given. So I don't routinely recommend this is done for every dog because dogs love food, and, you know, food's a big incentive of coming into the practise and it, you know, softens the blow of having to have injections and blood tests and things. But if there is a dog who's had a particular issue with one drug and been, seemed to be more sensitive after it was given, I might advise starving when that drug is used subsequently.
Let's get on to actually giving the chemotherapy now. We've decided on the protocol. We've prepared ourselves for adverse effects and also made sure the owner is OK with these things.
And Ted is with us in the clinic before chemo. Now before chemo, we need to do 4 things to make sure we're happy to give the drug. We do a physical exam, including temperature and body weight.
We check the remission status. We checked the previous response to the drug. And then we look at the haematology.
Sometimes people think that it's all on the blood test, it's all on the haematology, oh his cell count's OK for us to give chemo, etc. And really that's only a small part of what we have to do. We want to make sure that the physical state of the dog hasn't changed.
If the owner says they're OK, do we agree with that? Is it the case they've lost an awful lot of weight? Is it the case that that they've come out of remission, Perhaps we've been treating them for a few weeks and the nodes are growing again.
We, we don't want to fall into the trap of just boshing on with the treatment if they've come out of remission, and sadly I do see that happening at times, that people think it's a protocol, and the word protocol seems to absolve us of the responsibility to think about things. I think we assume we're, it's a recipe and we'll get a defined outfit when it really isn't in every case. So we need to check the remission status and make sure it's still working and make sure we're justified to continue giving more chemotherapy.
We need to check if this dog or cat has had this drug before, what kind of fallout was reported? Were they fine? Did they have massive diarrhoea?
Did they have severe neutropenia, do we need to reduce the dose? And then finally we look at the haematology, and as I said, it's neutrophils and platelets that are most important. I think it's fine to run that on an in-house machine, but we do need to check a smear to make sure the machine isn't lying.
And as I've said, the decision to give chemo or not depends on all these factors, not just the bloods. If we said yes to give the chemo. Then we need to make sure we thoroughly check our workings in calculating the drugs.
And in my clinic, this was the sheet on the right here that we used to use. It walks you through the calculation, making sure you don't skip steps, and most importantly, I want 2 people to check 3 things. 2, the calculation sheet must have 2 signatures to say the calculation is correct.
Then 2 people must agree that the vial of drug you've got out is the same drug and the same concentration that is written up here. Then 2 people must agree that the syringe you've drawn up contains the correct volume of the drug as specified on the chemo sheet. Then these people sign at the bottom of the sheet to say they triple check, in other words, and treatment can be given.
When I worked at the Royal Veterinary College, we had a big oncology service and a big emergency and critical care service. And people sent us cases where they'd been given chemotherapy and something had gone wrong. And let me tell you, it's very rare for people to extravasate cytotoxic drugs.
We're all aware of it and we make sure that that doesn't happen. Most mistakes in giving chemotherapy are silly mistakes in calculation. For example, getting migs per kg mixed up with migs per metre squared, or for getting the calculated volume out by a factor of 10.
These things can be lethal, to a cat or a dog, and they're very silly little mistakes that are very easy to prevent. Once when you proceed to give chemotherapy safely, you need 3 things to protect yourself and your colleagues from these drugs. You need personal protective equipment like the chemo tested gown and chemo tested gloves we see on the right here.
Now, they do need to be chemo tested, they can't just be any old gown and any old gloves. We also need a laminar flow hood. Perfume cupboard.
Now who's got that in their practise? Very few people, but you know what? You could use it in someone else's practise.
You can buy preloaded syringes of chemotherapy drugs, and there are a number of companies that will send them to you with a courier, so you don't need a lamina flow hood in your practise. You could buy preloaded syringes of drugs drawn up in someone else's laminar flow hood. And finally you need to use the closed system transfer devices.
If you use the right PPE and the closed system transfer devices and you've bought preloaded syringes or you happen to have a fume cupboard in your practise, then that should be all you need. It's not strictly essential to have goggles and a respirator if you're using a closed system transfer device, but as a belt and braces measure, we recommend a goggles and a respirator as well. What am I talking about when I'm talking about closed system transfer devices?
Well, these things, and there's lots of brands. Previously I've used the seal up here. And currently my colleagues and I are using TV adapter.
Lots of other people use Kema Clave and EquaShield as well. Other brands are available. Now I'll show you how simple it is to draw up the drug using a file system.
And pretty much all these manufacturers of the different systems do have videos online, showing how their specific system will be drawn up as well. So to start with, in the fume cupboard, we will place one of these white, satellite dish looking adapters onto the vial of cytotoxic drug. Step one, We then get a lure lock syringe and we screw this adapter here onto the top of it.
This adapter has teeth a bit like a, a light bulb does. And then what you do is you put this light bulb adapter onto the onto the kind of indentation on the top of the cytotoxic vial, you push and you twist just like a bayonet light bulb fitting. You'll see that the adapter on the syringe has this blue bit here.
Now when you can see the blue bit visible, it means there is a block in the communication between what's in the vial and what's in the syringe. To be able to draw up drugs, you push the syringe in so you can't see the blue vial, and then the vial is connected to the syringe and you can draw it up. To administer, you place an intravenous cannula by first stick.
If it's not first stick, please replace the cannula somewhere else. And then apply one of these special ACLT connectors, and it's got a little, receiver there. That is the perfect reciprocal fit of the adapter on your syringe.
The You attach this to the cannula. And then you see two ports on the T connector, you've got the, the one here with a conventional attachment that you can attach a lure lock syringe full of saline and that's your flash. And then for this one here, you see we have attached the cytotoxic drug.
With the stem pulled back. So it's not communicating with the vein. When you're happy with the placements and everything's in order, you push the syringe in.
Like that, and now in the picture on the right, the contents of the syringe, the cytotoxic drug, are connected to the dog's circulation. And you can start to give it If the dog starts moving or becomes unsettled, all you need to do is pull the stem out again to disconnect the contents of the syringe from the circulation, and you're safe. So to give the drug We, First, sorry, what we do is we inject the contents of the syringe.
And then we have to wash the syringe to make sure all the molecules of the drug that we intend to go into the dog get in the dog. And we do that by kinking the T connector on the dog's side. We might kink the key connector up here.
And we flush the saline from the big sy flush syringe into the small cytotoxic syringe. Then we block off the flush syringe again and Push the contents of the syringe, of the small syringe back into the dog like that. Now my nursing colleagues have created this video to give a few tips with some of the catheter placement and things.
So we've got a first stick IV catheter here. And we're going to secure it using see-through medical tape. You can order this from a normal wholesaler.
Note though that she's not going underneath the catheter, she's just going over the top. We don't want this to stay in for 3 days unsupervised. We need to stay in for a few minutes supervised, and it's much easier to get off without risking flicking drug if you've just gone over the top.
She's also folded over a bit so it's easier to remove wearing gloves. Now attached the T connector. We're putting a 2nd bit of tape on at an angle.
Can you see that? That's at an angle, in case the dog pulls his leg back, it gives some resistance against pulling back, and then we've got a third bit more distally. When we're giving treatment, we use an absorbent cytotoxic tested mat underneath the leg.
If you haven't got that, an inkop pad's just as good, but note we've got everything we need there, including stuff we need to take the catheter out like swabs and vet wrap. We've got the cytotoxic drug, got the cytotoxic flush ready. And finally, after the chemo's given, when we're removing the catheter, we put some wet swabs hold firmly over the leg.
And some wet swabs in your hand as you take the catheter out. So the idea is you shouldn't see the catheter tip. The catheter tip will always be contained in the wet swab, and then that's put in the rubbish bag which is waiting while your assistant's holding the wet swab in place.
After a minute or so, the wet swab's removed and a dry swab is replaced, and the wet swab goes in the, rubbish bag and then, We're folding up the absorbent mat from the edges in. To avoid contaminating the table. I guess this bit where you remove the catheter, we've got cytotoxic blood that may splash in our face, is the most important bit to get right and the most common bit for people to get wrong.
So we need to make sure that we don't see the catheter tip and it's covered with these wet swabs, and we take care to do that. Finally, you can see that it's in a, a bag that pops tight. And after all the rubbish is in there, then the bag will be just popped, sealed again, and put in cytotoxic waste.
Note that gowns are not going in, if gowns haven't got fluid on them, blood or drug or whatever, then they could be reused a few more times. Well we're giving vincristine to Ted, we need to be aware of what to do if for something, some reason something goes wrong and a bit of drug gets extravasated, OK? Now it is a drug specific approach to extravasation.
And if we're going to give these drugs, I would have on hand. A list of things we need to do if it does get extravasated. It's quite easy for Vincristine, we give some steroids, which he's probably on anyway, systemic or topical.
We'll give some other analgesia, for example, paracetamol, and we might want to use things like aloe vera cream. After it's happened, we, we put some saline locally and we apply some heat packs to try to spread out to dilute the vincristine that's extravasated, and something that can help further is hyaluronidase, which helps to break down some of the, Fascia, and allows the, the drug to spread out further. It's very rare to get a severe EchR after extravasation of pristine because typically it's only a small amount that's extravasated and if you act on it promptly, you're unlikely to have a, have a problem.
When we give cyclophosphamide to Ted. We'll usually dispense this to give at home or sometimes you might be happy given in the clinic. Just gotta make people aware that we don't crush or suspend oral medications.
We can't halve the tablets. We don't want to break them. We don't want to do anything that will make a little powder.
So what I would do is make sure you order in resized or reformulated oral medications and whoever's giving it knows that they need to wear chemo tested drugs. And then it needs to go down without touching the sides. However you do that, and it can't be chewed, bitten, crushed, or split.
With oral chemotherapy, it's even more important to wear PPE including the respirator and the goggles, and they're essential this time. There's no equivalent to the closed system transfer device for oral chemotherapy, so it is essential to wear the right PPE. And this brings me on to the bigger subject, the cytotoxic drug safety in general.
Now, we know that cytotoxic drugs can interfere with DNA cell growth, and division, and potentially these things are mutagenic, carcinogenic, teratogenic, and abortive fashion. We know this from studies of lab animals, and we know this from in vitro studies of cell lines. When we look at what's actually happened to people who've been exposed to lots of chemotherapy, then it's, it's not so obvious actually.
We know people who've had chemotherapy for as a treatment themselves have a risk of developing a completely unrelated cancer later in life, and that's particularly with drugs like doxorubicin or cyclophosphamide, and it seems to be proportional to the amount of chemo that they've had. Excuse me. In human, in humans though, nurses who were giving chemo without any PPE or any safety precautions were compared to the general population.
And they did have a higher level of chromosomal abnormalities, and they did have a higher level of excretion of cytotoxic drugs and metabolites. And there may have been a subtle increase in risk of abortions. And some canvas.
But most of these studies were actually performed before we were using closed system transfer devices like we do today, and they didn't really account for other lifestyle based factors like smoking. When you actually look at the studies, you see that any difference was really quite subtle. In this one, if you look at the green underlined.
No significant association was detected between exposure to drugs and congenital malformations or stillbirths. But there was an association between chemo and spontaneous abortions, but if you look at the odds ratio, it's really, it's quite low. So this study identified a small incremental risk for damage to pregnancies in female staff working with cytotoxic drugs.
In this study here, they found that there was a risk of breast cancer when we use some statistics and congenital abnormalities of the eye in children. But That wasn't true when you used a different statistical test, and in that test there was a slightly increased risk of cancer of the rectum. Many things they tested for weren't statistically different.
So I think we can conclude that, yeah, there, there is a risk of unprotected exposure to chemotherapy drugs, but It's not quite as big as we might have been worried about. We still have to protect ourselves from these drugs. But when you compare it to smoking, The risk pales to a very, very small level.
These are some of the studies on smoking which show quite a categoric and very damning effect of smoking on the body. So to summarise then, repeated low level contact with tioplastic agents has never been shown to increase the risk of cancer at the moment. But we know that cytotoxic drugs can increase the risk of cancer and be damaging to pregnancies, so there's still cogent reason to make sure the exposure of the non-patients is prevented.
And this is quite important when we consider studies like this, which shows that, you know what, we, we vets, we British vets in this study. Are pretty rubbish with psychotoxic drug safety. Standards of administration of cytotoxic drugs was followed by 2% of the vets giving chemo.
Training was inadequate in over 50%. And some examples include 60% of vets were using just normal infusion kits, 2/3 were using normal gloves, 50% used normal surgical gowns, some were even given chemo in the consult room with the owner. And in this study from Holland, it showed that Dutch vets aren't much better, I'm afraid.
The study actually looked at 8, work sectors with potential exposure to cytotoxic drugs, like they looked at care homes, laundry services, care assistants, stuff like that, and they soon honed in on veterinary medicine because the results were much more interesting, stroke worrying in veterinary medicine. On the gloves after administration, chemo residues were 15 times higher than levels measured after administration in hospital. And you've got to think in hospitals they give higher doses of drugs and they use drugs much more frequently, give it to many more patients, whereas in a vets it would just be one or perhaps two patients on treatment.
And in this study from Germany, They swabbed areas in a hospital for platinum drugs, and if you look at these things underlined in red here, they are, you know, some up to 10 times greater than some of the references from the hospital on the right, human hospital. So quite rightly, the ACVIM have produced a consensus statement on safe use of cytotoxics in practise, and there is an older European version as well. These are open access, and I suggest you have a look at them if you want to start giving chemotherapy in practise and keep a copy, copy for reference in your clinic.
When you're considering protecting staff from chemotherapy drugs, you need to consider the route the drugs will take from when they come in the building. To when they leave You might think, well, it's OK, it's just me and one of my colleagues who need to be aware of it, but Bear in mind studies like this. Who unpacks the order?
Is that you? Is that your colleague? Because in this study here, 56% of chemotherapy vials from a whole host of different manufacturers had contamination of cytotoxic drugs on the surface.
And is it qualified vets and senior nurses unpack the order? If, say there's a shelf that falls down or a cat escapes and starts knocking things off the shelves. Who is it who clears up the mess?
Is that a qualified vet or a senior nurse? So when we consider exposure to cytotoxic drugs and look at what could potentially go wrong at all these steps, we soon conclude that pretty much all staff have to be protected. So some specific advice I have for you is that all people whoo or restock the area, unpacked boxes are aware of the risks and the protocol to follow with spills.
When you give chemotherapy, try to designate a chemotherapy area with limited footfall out of it. Particularly you need to plan and have everything in it before you start the process. What we don't want to see is people wearing a chemo gown and chemo gloves.
Leaving the area, running across the prep room to a fridge to get a bottle of Moropotent or dexamethasone or something like that, these things need to be in the area from the start. And something that you could, that is very helpful because we know that there's all kinds of things on the floor of a veterinary practise, something that can help to protect yourself is have shoes that you wear for work, that stay in work. And you wear different shoes home.
It would be even better if you change at work and make sure your clothes are laundered, every day, but we don't tend to launder our shoes every day. And we know that there's all kinds of things, not least, multi-resistant, bacteria on the floor of most veterinary practises because there's a lot of antibiotics going on in the environment, and they, could be carried home on shoes, and also traces of drug and cytotoxic drug and bodily fluids could be found on shoes. So it's a really good and easy idea to have your work shoes that stay in work and your home shoes that stay at home.
And to make sure that we don't scrimp and save on the chemo tested PPE that we're using. Finally, pregnant or nursing people should not be involved in the handling of drugs, giving chemo or nursing sick animals who have had chemo, to any degree. Pregnant or nursing people should be dealing with other things, just in view of the, of the potential damage to pregnancy.
So this is the setup I had in my last hospital, which was actually a converted body shed. It was a little annex to the kennels, but we've got everything there that we need. Had all the necessary equipment.
If you look in the picture on the right, it doesn't necessarily have to have a fume hood because we could have bought preloaded syringes, but since we dealt with chemo a lot, we had our own hood. Got the fridge there. And we've got the cupboards where the consumables and the oral drugs are stored.
On the walls, we have protocols for what to do if there's an extravasation or a cytotoxic spill. And we've got all the PPE, in a little cup cupboard behind where we can see. We've got good lighting, we've got tables, and we've got a, a small kennel.
So let's go back to this slide, we know that we can avoid the laminar flow hood using preloaded syringes, we've got the PPE and we've got the closed system transfer devices. After chemotherapy, the patient is now cytotoxic and it's their body fluids that should be considered contaminated. We know this, we'll protect ourselves.
But does the person who will be cleaning out the kennel know this? Does the person who'll be handing out the dog to the owner or perhaps taking him out in the back to urinate know this? So we've made some laminated sheets just saying.
What you have to do with this patient, how you wear PPE and wear gloves, and how certain people, the pregnant or nursing people, should get someone else to do, to deal with that animal on their behalf. And the patient will remain cytotoxic for a certain period, and this is different for every drug. If you look at vincristine, the 2nd up from the bottom.
You'll get vincristine in the urine for 3 days and you know, you know, up to about 6 days in serum and then you should be fine. You're giving other drugs, for example, carboplatin, you can find that in the urine for up to 3 weeks. So the cytotoxic period does, does vary an awful lot.
And you also need to make sure that what you're doing with the cytotoxic rubbish complies with, what the disposal company, wants you to do. Most cytotoxic waste is purple but not all, so you need to use the right bags and the right bins in accordance with your contractor. And I want to show you that the system works.
If you use the PPE, the closed system transfer devices. And you make sure that you either buy preloaded syringes or have used the fume hood. Then the exposure to drugs, is absolutely abrogated.
Look at this study here I showed you earlier. The red underlines are from the swabbing when vets were giving chemo without using a closed system transfer device, and these green ones 9 months afterwards show either an acceptable level or no detectable level of drugs in the same place. So the closed system transfer devices are transformative.
They really do work and I don't think we should be giving cytotoxic drugs without them. There's another study here, of 20 specialty hospitals in the US that were all given lots and lots of chemotherapy. And they swabbed the environment for carboplatin, doxorubicin, vincristine, and cyclophosphamide, and they found no contamination with carboplatin, doxorubicin, or vincristine, none at all.
On a point that's slightly different though, 4 out of 20 hospitals were contaminated with cyclophosphamide, and my question to you is what's different with cyclophosphamide? Well, cyclophosphamide is an oral drug, mostly, it can be injectable, but mostly it's given orally. So this tells us two things.
It tells us that these closed system transfer devices and appropriate systems in place work. And will mean there's no risk for us providing these things are used as they intended to be and that the appropriate health and safety protocols are in place. However, giving oral drugs is harder.
There's no closed system transfer device for cyclophosphamide orally. So we have to be very, very careful giving these, and I think the best tip I can give you is. To, be very, very, disciplined in when you're tableting an animal.
There are some people, and every practise there's at least one of these, who will never be beaten by a tough cat, and if the cat spits a pill out, they'll get the pill and they'll say, right, we'll have another go, we'll put it back in. And while I do admire the, you know, the skills and the bravery of people like that, that's not something to do with cytotoxic drugs. If a cat has spat out a pill, a pill will often be a bit chewed and weakened, a bit soggy and further weakened.
And if that pill perforates, you'll get a kind of a cloud of cytotoxic dust that's very difficult to deal with. And that's where we end up contaminating the environment. So if a cat's difficult for a pill, please change something.
Make sure you change your handling, your handler, your situation, you let the cat rest. You might want to pre-med him or her with gabapentin and take a bit longer to do it to give them time to chill out. If a pill's been in and spat out again, we want to change that.
We want to throw it away in a sealed bag in inside the toxic waste and use another one because it's the soggy and pre-chewed pills that tend to break. And finally our clients need to know this risk too. After the dog's had chemo, he or she will have metabolites of cytotoxic drugs in their bodily fluids and not least their urine and their fecess.
We don't want to expose ourselves to any of these. It might be we're using Oral drugs that we're giving the owners to give at home like cyclophosphamide for example, and they need to be OK with handling those wearing chemo-tested gloves and making sure the tablets aren't broken or crushed. So we do tell them to designate a toileting area in the garden and to double bag faeces.
We tell them to clean vomit, urine wearing double gloves using bleach, bleach-based detergent if possible. Bleach will help to denature the metabolites of chemo drugs. If the dog, does their business on concrete outside and washed down with copious amounts of water.
And please make sure that if people are pregnant or breastfeeding, they're not involved with dealing with excreta or dealing with medications. Please also bear in mind that the TKI drugs like Massivet and Palladia are not any safer. People frequently think they are, they seem inherently much less scary, but they're really not any safer and we need the same precautions with these.
And so after all said and done, you do get some clients. You say, actually no, no, I'm, I'm not comfortable with the risks. I don't want any chemotherapy used in my dog or cat.
And it helps in situations like that to put things into perspective a little. Because So, no, the, we, to date, no case of human cancer has been shown to have occurred. Due to low level exposure to cytotoxic drugs over a certain period, yet every year there are cases of horrible zoonotic disease.
Toxicara canis can cause blindness and epilepsy in children. Teena hydatogenia may need people to have a liver lobectomy. Salmonella and Campylobacter can be found in normal dog faeces, and that can put you or me in hospital on a drip, and leptospirosis can put us on the renal transplant waiting list.
If you're worried about damage to a pregnancy, then look no further than toxoplasma or chlamydia, incredibly common and found in nearly every cat out there, and the list goes on and the list goes on and the list goes on. So zoonotic infections do occur. Any risk from exposure to metabolites of chemotherapy drugs in a dog or a cat.
I've not really. Being characterised, we know theoretically there's a risk, but it does seem to be a theoretical thing. And so the risk of infectious disease is always bigger.
And if people are viewing things in a world of probability rather than possibility, it helps, and perhaps some people should think, you know what, I'm going to get less frantic and less hysterical about the risks of the psychotoxic drugs, and instead, I'm going to stop my dog giving me big wet kisses on my face. That would be a much better and pragmatic approach to to dealing with, living with a dog or a cat. In summary then It's fine to use the 2nd best treatment, providing we are transparent about the risks and efficacy when the client's fully on board with the decision.
All you need to handle chemotherapy safely is appropriate PPE, a closed system transfer device, a fume cupboard, or other redrawn medication. And trained staff. Giving chemotherapy safely requires a first stick intravenous catheter, good restraint, and appropriate knowledge of the drug and the system you're using.
Chemotherapy side effects are principally gastrointestinal and haematological, though drug side effects, drug specific side effects are possible. And protecting ourselves against chemotherapy exposure involves educating everyone who may come into contact at every step of the drug's path through the building and educating owners, and please remember that it's the oral medications that are the most important risk for self-exposure. If you're interested in staying up to date in oncology, the veterinary cytology Facebook page is really interesting to look at, and please check out ESBON as well, which has an annual congress every year at the end of May, usually in nice locations, and it's a very welcoming, diverse and inclusive group of vets from first opinion, specialty practise, pathology, surgery, etc.
That's me, that's where I work, at Bristol Vet specialists. I'd like to acknowledge the team. I couldn't do anything I do without their support.
And I'd like to thank the webinar vet for asking me to speak and thanking you ever so much for tuning in to listen. Hope you have a good day.