Bisphosphonates for Osteosarcoma

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Sat, 02 Oct 2010 11:33:41 GMT

I forgot to post the response to the Zometa in this dog. No change at all. Never mind, worth a go!

If anyone wants to use it in the future I'd advise contacting Novartis's human side who sold it to us and dispatched it for £180 a bottle, significantly cheaper than it would have been from NVS. You normally need to pay for it before they will send it although when I phoned them the duty manager that day liked dogs so sent it to us before payment had cleared. They're not set up to take credit card payments so you need to post them a cheque.

Re: Bisphosphonates for Osteosarcoma

Malcolm Ness — Thu, 15 Jul 2010 10:04:59 GMT

I agree completely with Alex.

My understanding is that the increased survival time with chemo is currently estimated in days-to-weeks and possibly weeks-to-months but certainly not months-to-years. The platins are fortunately not terribly nasty drugs so increased patient morbidity is not really a barrier to their use.

I have done limb sparing surgery for other reasons (non-malignant or less malignant osteodestructive lesions) and the convalescence is long. The orthopaedic outcome of limb-sparing done on osteosarc cases does not stand up to close scrutiny and if we do find a way of getting these dogs to live longer, we will have to look again at the orthopaedics - currently it seems that most of these dogs die before their leg falls apart.

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 21:50:10 GMT

From a medical point of view, I think the evidence points to an increased survival time with amputation and follow up chemo compared to amputation alone in dogs without gross mets. It may not be a great increase in survival time, but then a few months may be a lot to a dog. It then comes down to is it worth it financially (owner decision) and for the side effects. I find carboplatin has remarkably few side effects. I have had three dogs on it in the last couple of months, and not one had a noticeable side effect. One got marginally neutropaenic, but it wasnt symptomatic with it.

I'm not a fan of limb sparing surgery, and if it didnt come across, not really a fan of palliative analgesia with bisphosphonates or other treatments. We can stop these dogs hurting completely with amputation.

Alex

Re: Bisphosphonates for Osteosarcoma

Vikki Halliday LLB — Wed, 14 Jul 2010 20:26:07 GMT

[quote user="Malcolm Ness"] "sell" the procedure as surgical analgaesia and have a seperate discussion about chemo etc - most cases get amputation then later euthatal as the benefit of even agressive chemo is, as yet, not massive.[/quote]

Refreshing point of view Malcolm. So how do you personally feel about "limb sparing" techniques and mop up chemo currently offered? Most of the current oncology centres seem keen to go down this route rather than what I feel is the more pragmatic approach you suggest.

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Wed, 14 Jul 2010 20:06:51 GMT

Alex and Malcolm, thanks for your input. We've ordered a vial already and can't send it back so I'll give it and see what response we get. If it's not great then I'll discuss amputation again with the owners.

It's not walking on 3 legs yet, and if it did I'd use this as evidence to the owners that it would do OK with an amputation anyway, or would at least be worth a try.

Re: Bisphosphonates for Osteosarcoma

Malcolm Ness — Wed, 14 Jul 2010 19:25:27 GMT

I find that most dogs do better than you think they will, even the extremely big ones.

Pain control in bone cancer is rarely effective and many of these patients are functional tripods carrying a painful limb. Discussion with people managing bone cancer in humans indicates that these tumours hurt all the time and not just under weight bearing so I need little persuasion to amputate. We always look for lung mets and if we see any then we won't go for amputation as the end is probably very near.If chest looks clear O is advised that that is because we can't see them and not because they aren't there but on the assumption that in a dog with a clear looking chest, the end is probably less near, we will amputate. The dog is often obviously less painful on anaesthetic recovery and most dogs will hop around happily for a few pain free months before development of symptoms related to lung mets lead to euth.

I "sell" the procedure as surgical analgaesia and have a seperate discussion about chemo etc - most cases get amputation then later euthatal as the benefit of even agressive chemo is, as yet, not massive.

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 18:03:57 GMT

As a follow up, this is from a paper by the same authors above from the Vet Rec in 2000, where they did the force plate analysis they had previously discussed:

To dog owners this initial decrease in ability to brake after

a forelimb amputation, may suggest that the dog is less able

to cope with its new situation. Comments by owners during

previous research (Kirpensteijn and others 1999) suggested

that, at first, dogs with forelimb amputations have more difficulty

in keeping their balance, and fall more often, whereas

dogs with hindlimb amputations have more difficulty in gaining

speed. These comments can be explained by the results

of this study. The ability to brake decreases after a forelimb

has been amputated and this may cause coordination problems

during the period shortly after surgery. Owners should

be warned that dogs may at first appear to have more difficulty

in recovering from a forelimb amputation than from a

hindlimb amputation. However, the difference decreases over

time and does not result in a significantly different adaptation

time (Kirpensteijn and others 1999).

Dogs are thought to compensate for the loss

Although the centre of gravity changes after a forelimb

amputation, each hindlimb carries 27 per cent of the weight,

while the remaining forelimb carries 46 per cent. After a

hindlimb amputation, the remaining hindlimb carries 26 per

cent of the load, while each forelimb carries 37 per cent. This

result shows that a forelimb amputation places greater stress

on the remaining forelimb than a hindlimb amputation

places on the remaining hindlimb. It would be expected that,

because of this increased stress on the limb opposite to the

amputated limb, large breed dogs would have more difficulty

in adapting after the amputation of a forelimb than of a

hindlimb. However, this conclusion contradicts the findings

of the authors' previous study in which no significant association

was observed between the weight of the dogs and their

speed of adaptation (Kirpensteijn and others 1999). Most

dogs are able to shift their centre of gravity away from the

amputation over a period of time (Leach 1993).

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 18:03:55 GMT

As a follow up, this is from a paper by the same authors above from the Vet Rec in 2000, where they did the force plate analysis they had previously discussed:

To dog owners this initial decrease in ability to brake after

a forelimb amputation, may suggest that the dog is less able

to cope with its new situation. Comments by owners during

previous research (Kirpensteijn and others 1999) suggested

that, at first, dogs with forelimb amputations have more difficulty

in keeping their balance, and fall more often, whereas

dogs with hindlimb amputations have more difficulty in gaining

speed. These comments can be explained by the results

of this study. The ability to brake decreases after a forelimb

has been amputated and this may cause coordination problems

during the period shortly after surgery. Owners should

be warned that dogs may at first appear to have more difficulty

in recovering from a forelimb amputation than from a

hindlimb amputation. However, the difference decreases over

time and does not result in a significantly different adaptation

time (Kirpensteijn and others 1999).

Dogs are thought to compensate for the loss

Although the centre of gravity changes after a forelimb

amputation, each hindlimb carries 27 per cent of the weight,

while the remaining forelimb carries 46 per cent. After a

hindlimb amputation, the remaining hindlimb carries 26 per

cent of the load, while each forelimb carries 37 per cent. This

result shows that a forelimb amputation places greater stress

on the remaining forelimb than a hindlimb amputation

places on the remaining hindlimb. It would be expected that,

because of this increased stress on the limb opposite to the

amputated limb, large breed dogs would have more difficulty

in adapting after the amputation of a forelimb than of a

hindlimb. However, this conclusion contradicts the findings

of the authors' previous study in which no significant association

was observed between the weight of the dogs and their

speed of adaptation (Kirpensteijn and others 1999). Most

dogs are able to shift their centre of gravity away from the

amputation over a period of time (Leach 1993).

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 18:02:02 GMT

[quote user="Malcolm Ness"]

[quote user="alex gough"]Eek sorry about the typesetting, not sure how to fix that![/quote]

I assumed it was poetic - the layout and rhythm reflecting the odd gait of the tripod dog!!

[/quote]

Yes - I should have gone with it being deliberate! What's your opinion on amputation of forelimbs of big dogs Malcolm, I suspect you have the most expertise in this area of anyone commenting in this thread?

Alex

Re: Bisphosphonates for Osteosarcoma

Evelyn Barbour-Hill — Wed, 14 Jul 2010 17:55:41 GMT

I like the bit about "the reaction of social acquaintances".

Re: Bisphosphonates for Osteosarcoma

Malcolm Ness — Wed, 14 Jul 2010 17:52:19 GMT

[quote user="alex gough"]Eek sorry about the typesetting, not sure how to fix that![/quote]

I assumed it was poetic - the layout and rhythm reflecting the odd gait of the tripod dog!!

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 17:47:28 GMT

Eek sorry about the typesetting, not sure how to fix that!

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 17:46:04 GMT

There are obviously different opinions about this, and different experiences, but it seems to be conventional wisdom that you dont amputate large breed dog's forelimbs, which isn't greatly supported by the evidence or the opinions of most surgeons these days (at least the ones I speak to and the comments I have read on VIN). A fairly old study in the Vet Rec reports owner satisfactions with amputation (see below). Personally, if it is at all possible, I would prefer to amputate the limb and have the dog pain free, than try to manage the pain. I think the Lab initially mentioned in this thread would be better off with amputation unless it has dreadful arthritis in the other leg, and I have certainly seen greyhounds with forelimb amputations that have done extremely well - would they be a similar size and conformation to your 45kg lurcher/wolfhound?

Alex

Vet Rec. January 1999;144(5):115-8.

J Kirpensteijn1, R van den Bos, N Endenburg

In this study, owners were questioned about the results of amputation in 44 dogs. 23 dogs were large breed, up to 60kg. 25 dogs had a forelimb amputation. 41 dogs showed a good adaptaion, and 1 showed an acceptable adaptation, still capable of half hour walks. 22 owners were originally against the amputation, and 19 afterwards described their objections as unfounded.

It goes on to state:

It is said that a large dog will have more trouble in adapting

walking on three limbs than a smaller dog (Brodey and

Abt 1976).

Half of the respondents had serious objections to

the amputation because of

the expected appearance of the

dog after the

surgery and the possible problems in adaptation.

The

results of this survey, however, do not support this

hypothesis. The

weight of the dogs had no significant association

with their speed of adaptation and therefore should

not

be a criterion in deciding whether to amputate a limb. In

the authors' experience, the

amputation of a limb of an old

dog

is often rejected because of expected problems in the

quality

and speed of adaptation. However, no significant association

was

observed between the age of a dog and the quality

and

speed of its adaptation, suggesting that age should also

not

be a criterion when deciding whether to amputate a limb.

However,

the reaction of social acquaintances will be significantly

more negative to an amputation in an older

dog.

Carberry and

Harvey (1987) stated that the function of the

dog would

not be influenced by whether a fore- or hindlimb

had been amputated. According to Budsberg and

others (1987)

the distribution of bodyweight

on each limb at standing is 30

per cent to each

forelimb and 20 per cent to each hindlimb,

suggesting that it might take longer to adapt to

walking on

three legs after the

amputation of a forelimb. However, the

statistical

analysis of the adaptation time and method of adaptation

this study does not support this view. Nevertheless,

the function of each individual limb

may change after any limb

amputation.

In the normal dog, the function of the forelimbs

in weight-bearing

and locomotion is different from that of the

hindlimbs.

The forelimbs make a significantly greater contribution

the braking phase of the walking gait, compared with

the

significantly larger contribution to the propulsion phase

made by the hindlimbs (Budsberg and others 1987, Jevens and

others

1993). A technique that is frequently used to analyse

normal

and abnormal gaits in dogs is force plate analysis

(Budsberg and

others 1987, 1988, Jevens and others 1993). This

technique should be

useful for analysing the gait of dogs on

three limbs and

make it possible to analyse the influence of the

amputated

limb on the functional status and changes in

weight-bearing by the

dog after the amputation.

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Wed, 14 Jul 2010 16:08:42 GMT

I spoke to Tom Cave about this particular case and his experience with wolfhound type dogs and forelimb amputation wasn't good and the owners aren't keen on this either, but I guess you don't know until you've tried it in each individual.

Re: Bisphosphonates for Osteosarcoma

Alex Gough — Wed, 14 Jul 2010 15:18:49 GMT

Doxorubicin and/or carboplatin are indicated as follow up treatment to amputation as Laurence said. I like carboplatin - seems to be very well tolerated. My understanding from surgeons is also that we shouldnt be shying away from forelimb amputation in large and giant breed dogs too unless there is a lot of orthopaedic disease in the other forelimb. Although the forelimb carries more weight, it is more important at braking, so dogs with one front leg brake worse than dogs with four legs, whereas dogs with one hind limb accelerate worse than dogs with four legs.

Alex

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Wed, 14 Jul 2010 14:59:18 GMT

As I understand it, chemotherapy won't do much about the primary for osteosarcomas.

If you amputate/have limb sparing surgery then chemo is indicated to try to mop up microscopic metasteses to extend life expectancy. Without surgery the thing that's going to lead to a descision to euthanase will be uncontrollable pain or pathological fracture at the primary site.

In this case it's the dog's comformation and size that makes me feel it will not cope well with forelimb amputation. Financial constraints mean that limb sparing surgery and chemo are not possible. Although the zoledronic acid is very expensive it is still affordable under the insurance so worth a go as meloxicam/tramadolparacetemol isn't working

Re: Bisphosphonates for Osteosarcoma

Martin Atkinson — Wed, 14 Jul 2010 14:49:42 GMT

I noticed no-ones mentioned chemotherapy in these cases: doxorubicin, cisplatin etc. Are you guys using biphosphonates & tramadol etc in addition or does no-one use chemo any more on these?

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Wed, 14 Jul 2010 09:06:24 GMT

I'm just about to try zoledronic acid for the first time, which will be interesting. It's used in humans for metastatic breast cancer amongst other things.

The dog is a 45kg lurcher/wolfhound affair with a distal radial osteosarc. I don't think it will do well if we amputate due to size and comformation. The dog is insured but they don't have enough cover to fund limb sparing surgery but we have enough to pay for 3-4 treatments (it's given by infusion once monthly if it is effective).

And yes, the price is astronomical. The cost price for the Zometa is £278 + vat for 1 4mg vial. We're not marking the drug price up but we're charging for the IV infusion and time spent doing it to make it more affordable. If it works really well and the owner runs out of insurance cover they're going to have to decide whether to continue funding it themselves or just to be grateful for an extended time of quality life. Alternatively it might do nothing!

A cheaper alternative suggested to me is alendronic acid (Fosamax) tablets. It's used for osteoporosis and isn't as potent so is less likely to have a good response, but it's cheaper - NVS have it listed at about £30 for a box of 28 tablets I think, which would provide a month's treatment.

Re: Bisphosphonates for Osteosarcoma

Bob Russell — Fri, 14 May 2010 10:39:13 GMT

I understood, in my very unscientific way that the idea behind these drugs was to slow the bone destruction side of things, to strengthen (or slow down the weakening) of bone. The pain relief I assumed was linked to improved bone strength rather than pain relief. I am more than happy to be corrected if I am wrong.

Re: Bisphosphonates for Osteosarcoma

Vikki Halliday LLB — Fri, 14 May 2010 08:57:55 GMT

[quote user="Michael Woodhouse"]

I'd be more worried about the bone tumour that is going to kill the dog, myself. Keep the poor bugger comfortable. If it can't handle the pain killers then it will have to be put to sleep.

[/quote]

And for once I agree with you Michael!

Re: Bisphosphonates for Osteosarcoma

Vikki Halliday LLB — Fri, 14 May 2010 08:57:02 GMT

I would echo completely the comments about using Meloxicam and Tramadol, as I have done so at maximum doses in similar osteosarcoma cases with no GI side effects.

Unfortunately the main reason I end up euthanasing these dogs is when they suffer a pathological fracture at the tumour site, and then the Tramadol can sometimes mask some of the lameness, so you need to be careful.

Re: Bisphosphonates for Osteosarcoma

Hanna Bennett — Thu, 13 May 2010 20:57:45 GMT

only used it once - pamidronate - on a Rottie. Some benefit, but not massive really. Ended up amputating, and the dog was immediately pain free, and lived another three happy months. Not for everyone I'm sure, and you have to be very careful about renal damage. Oh, and very expensive!

Re: Bisphosphonates for Osteosarcoma

Bob Russell — Thu, 13 May 2010 15:52:06 GMT

We used zolidronic acid a few years ago (we got it cheap from the local hospital by chance). The short term results were actually quite impressive. The dog (a Gt Dane) became significantly less lame (on same level of pain relief) and we all felt had a better quality of life. We changed to Pamidronate when we ran out - the dog quite rapidly deteriorated after that but this may have been coincidence.

I do not think it changed the length of life by much but did seem to make the dog a lot more comfortable. There were no side effects noticed other than a very hefty bill - paid for by the insurance company.

On balance I would use it again but the cost is astronomical so make sure the owners are on board. We were honest with the owners that it was unlikely to extend life.

Re: Bisphosphonates for Osteosarcoma

Rob Reid — Thu, 13 May 2010 12:32:51 GMT

I have been using tramadol in combination with both NSAIDs and steroids for about 4 years now. The dose range is quite variable (1-5mg/kg up to TID) but I find it to be a very effective analgesic. I don't feel that I am seeing any increase in cases of GI ulceration etc, the only thing I find is that it can sometimes make dogs a little constipated. I don't have any personal experience using biphosphonates, but if this were my case I would be going with NSAID & tramadol. As an earlier post suggets, I would be more worried about keeping the patient comfortable than anything else.

Re: Bisphosphonates for Osteosarcoma

Laurence Webb — Thu, 13 May 2010 12:16:00 GMT

I use NSAIDs and Tramadol in combination quite happily and this is a case where quality of life is of more important than concerns about possible (unlikely) side effects. For that matter you could chuck in some paracetemol as well if you want and potentially more opioids.

I've not used bisphosphonates personally but I've referred dogs that have had them. I know they're hugely expensive but can be quite effective.

Try talking to Tom Cave for more advice http://www.cavereferrals.com/contactus.html