Gleevec And Osteosarcoma

[ahicks51]

I've seen a couple of trials in progress with Gleevec (imatinib) for use with osteosarcoma, mainly in small children.

 

Gleevec works by knocking out an enzyme (tyrosine kinase), and was originally developed for a certain type of stomach cancer that is very difficult to treat. Later it turned out to work well enough to label it for use with a certain type of leukemia.

 

Of course, the cost is awful- but it comes with side-effects that make it preferable to other forms of treatment.

 

Anyone know if imatinib has ever been tried- singly or in conjunction with other chemo- on osteosarcoma in dogs?

[HopeForHounds]

No idea, I will ask Dr Couto that when I see him. Or if you like email OSU and ask.

[Guest grey_dreams]

Interesting information!

 

I did some searches:

 

PCR analysis of canine mast cell tumors showed that they contain mutations in c-kit, so treatment with imatinib would likely inhibit tumor growth.

Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs.

 

Imatinib caused regression of canine mast cell tumors that were transplanted into immunodeficient mice, indicating that it potentially would be a useful treatment in dogs.

The tyrosine kinase inhibitor imatinib [sTI571] induces regression of xenografted canine mast cell tumors in SCID mice.

 

I found 2 cases where imatinib has been used to treat feline tumors. Both were successful.

Identification of a c-kit exon 8 internal tandem duplication in a feline mast cell tumor case and its favorable response to the tyrosine kinase inhibitor imatinib mesylate.

A phase I clinical trial evaluating imatinib mesylate (Gleevec) in tumor-bearing cats.

 

 

A search at The Ohio State University Greyhound Health and Wellness Program gave no results. It seems like the vet research community should soon be (or already are) testing imatinib in vivo for dog tumors.

 

[ahicks51]

 

Wow! Thanks, grey_dreams!

 

No idea, I will ask Dr Couto that when I see him. Or if you like email OSU and ask.

 

If it comes up, that'd be great. I'd feel guilty about emailing the guy, as I'm sure he is a busy, busy man.

[HopeForHounds]

Wow! Thanks, grey_dreams!

 

No idea, I will ask Dr Couto that when I see him. Or if you like email OSU and ask.

 

If it comes up, that'd be great. I'd feel guilty about emailing the guy, as I'm sure he is a busy, busy man.

 

He is, but always happy to answer reasonable questions.

[fritofeet]

I've seen a couple of trials in progress with Gleevec (imatinib) for use with osteosarcoma, mainly in small children.

 

Gleevec works by knocking out an enzyme (tyrosine kinase), and was originally developed for a certain type of stomach cancer that is very difficult to treat. Later it turned out to work well enough to label it for use with a certain type of leukemia.

 

Of course, the cost is awful- but it comes with side-effects that make it preferable to other forms of treatment.

 

Anyone know if imatinib has ever been tried- singly or in conjunction with other chemo- on osteosarcoma in dogs?

 

 

I don't have any experience in the dog dept, but that is what my Dad was taking, and holy cow it is expensive. His bill without insurance was over $30k per year, and luckily Novartis provided it for him until the insurance kicked in. It probably has reduced in cost, but it would not be an option for treatment for a lot of people. Even though the side effects are not terrible compared to a lot of products, there were still some very uncomfortable ones for my Dad. Another thing that can happen, is the Gleevec resistance that is where the cancer mutates enough to get around the specific enzyme inhibitor, and the cancer comes back twice as fierce. Not to be a negative Nellie or anything, but thought you might want some info from the human end.

[ahicks51]

I've seen a couple of trials in progress with Gleevec (imatinib) for use with osteosarcoma, mainly in small children.

 

Gleevec works by knocking out an enzyme (tyrosine kinase), and was originally developed for a certain type of stomach cancer that is very difficult to treat. Later it turned out to work well enough to label it for use with a certain type of leukemia.

 

Of course, the cost is awful- but it comes with side-effects that make it preferable to other forms of treatment.

 

Anyone know if imatinib has ever been tried- singly or in conjunction with other chemo- on osteosarcoma in dogs?

 

 

I don't have any experience in the dog dept, but that is what my Dad was taking, and holy cow it is expensive. His bill without insurance was over $30k per year, and luckily Novartis provided it for him until the insurance kicked in. It probably has reduced in cost, but it would not be an option for treatment for a lot of people. Even though the side effects are not terrible compared to a lot of products, there were still some very uncomfortable ones for my Dad. Another thing that can happen, is the Gleevec resistance that is where the cancer mutates enough to get around the specific enzyme inhibitor, and the cancer comes back twice as fierce. Not to be a negative Nellie or anything, but thought you might want some info from the human end.

 

I know it's horribly expensive. Out of curiosity, I poked around on some Canadian pharmacy sites- apparently there is a "generic" version (probably illegal as Novartis still has it under patent- they wouldn't allow a generic on the market) presumably made in India. I played around with a few numbers, and figure it'd probably run about $500-1000 per month for a dog-sized dose. But if used in conjunction with chemo, maybe only a few weeks' worth of the drug might improve survivability? I dunno.

 

[romansperson]

I expect we won't know any more about this until the price comes down. Just carboplatin alone is $500 a pop, and that doesn't include the vet's fees for administering it.

[fritofeet]

I know it's horribly expensive. Out of curiosity, I poked around on some Canadian pharmacy sites- apparently there is a "generic" version (probably illegal as Novartis still has it under patent- they wouldn't allow a generic on the market) presumably made in India. I played around with a few numbers, and figure it'd probably run about $500-1000 per month for a dog-sized dose. But if used in conjunction with chemo, maybe only a few weeks' worth of the drug might improve survivability? I dunno.

 

I'm not sure how long the dose period in conjuction with chemo would be. My Dad was told it would be something he had to take for the rest of his life. Dunno if that helps either...

[ahicks51]

I know it's horribly expensive. Out of curiosity, I poked around on some Canadian pharmacy sites- apparently there is a "generic" version (probably illegal as Novartis still has it under patent- they wouldn't allow a generic on the market) presumably made in India. I played around with a few numbers, and figure it'd probably run about $500-1000 per month for a dog-sized dose. But if used in conjunction with chemo, maybe only a few weeks' worth of the drug might improve survivability? I dunno.

 

I'm not sure how long the dose period in conjuction with chemo would be. My Dad was told it would be something he had to take for the rest of his life. Dunno if that helps either...

 

That's true- but as chemo is to literally poison the undesirable cells, using drugs that slow or halt growth of the same tissues, a 1-2 punch sort of thing- that could be valuable. If not Gleevec, then perhaps some of the anti-angiogenesis drugs, that sort of thing. Stuff with relatively low toxicity.

[Guest grey_dreams]

I expect we won't know any more about this until the price comes down. Just carboplatin alone is $500 a pop, and that doesn't include the vet's fees for administering it.

 

Actually, it works in the opposite way. The price is no deterrent for basic research on how useful the drug is for treatment of tumors. If the data from basic research shows that it is a useful drug, then it will start to be routinely used in a clinical setting. The more it is used, the more drug that is manufactured, and then the price starts to come down (also with the help of generics).

[romansperson]

I expect we won't know any more about this until the price comes down. Just carboplatin alone is $500 a pop, and that doesn't include the vet's fees for administering it.

 

Actually, it works in the opposite way. The price is no deterrent for basic research on how useful the drug is for treatment of tumors. If the data from basic research shows that it is a useful drug, then it will start to be routinely used in a clinical setting. The more it is used, the more drug that is manufactured, and then the price starts to come down (also with the help of generics).

 

What I was referring to was the initial cost of using it clinically. Not very many people are going to be able to afford such a treatment at the outset, particularly if it is in combination with any other drugs that are expensive. Carboplatin, as an example, will never be much (if any) cheaper, as it is a platinum compound. That means it will likely be a long time before a drug that like Gleevec is used routinely in pets (if it ever is).

 

Drugs produced by recombinant DNA technology (like Procrit and Neupogen). aren't going to get cheaper any time soon either - and those could potentially be useful in dogs for more reasons than just chemotherapy.

 

[ahicks51]

I expect we won't know any more about this until the price comes down. Just carboplatin alone is $500 a pop, and that doesn't include the vet's fees for administering it.

 

Actually, it works in the opposite way. The price is no deterrent for basic research on how useful the drug is for treatment of tumors. If the data from basic research shows that it is a useful drug, then it will start to be routinely used in a clinical setting. The more it is used, the more drug that is manufactured, and then the price starts to come down (also with the help of generics).

 

What I was referring to was the initial cost of using it clinically. Not very many people are going to be able to afford such a treatment at the outset, particularly if it is in combination with any other drugs that are expensive. Carboplatin, as an example, will never be much (if any) cheaper, as it is a platinum compound. That means it will likely be a long time before a drug that like Gleevec is used routinely in pets (if it ever is).

 

Drugs produced by recombinant DNA technology (like Procrit and Neupogen). aren't going to get cheaper any time soon either - and those could potentially be useful in dogs for more reasons than just chemotherapy.

 

I like what I'm seeing with the new-ish cancer vaccines for melanoma: administer it for free (in the trial stages), and watch its use proliferate. Once well-established in veterinary use, migrate to human applications and make some REAL money.

 

I'm betting if someone approached Novartis and asked for enough Gleevec for trials involving osteosarcoma in dogs, they might be amenable to free product, or at least greatly reduced cost. I seem to recall that Dr. Cuoto's research has implications for pediatric osteosarcoma- that's a pretty big "in." But that's just my opinion. I know nothing outside of vaccine trials in animals.

 

BTW: Carboplatin is about 1/2 platinum by weight (195 grams out of 371 per mole). At 500 mg/dose, a spot price of $1304 per troy ounce (about $42 per gram, current as of today), that 250 mg of platinum works out to $10.50 worth of platinum metal per dose. Not sure how much a dog gets, or how many doses are required. (And, yes- I've worked in industry and chemistry research- I know that $10.50 quickly becomes a much larger figure once other factors are considered- especially for medicine!)