Metacam for malignant melanoma?

Re: Metacam for malignant melanoma?

Martin Atkinson — Tue, 06 Jul 2010 10:26:25 GMT

Regarding the trustworthiness of histology reports: I think one still has to question the individual skill or experience of the pathologist reading the slides. With the dog I illustrated, the histo was done by Fynn Laboratories so should be trustworthy and I asked them to look at it again, the tissue didn't look grossly like a testis but histo suggested it was. So either I don't know 2 normal testes when I remove them - which after 35 years of castrating animals is rather unlikely, the pathologist was wrong or this dog was indeed over-endowed! I know which I think is the most likley scenario. And as another example, I have a cat with what for all the world clinically appears to be IBD and intestinal biopsies supported this but histo of the mesenteric lymph nodes said it had mast cell tumours. I don't have the exact wording from the report because it has been electronically scrambled in the bowels of the computer so can't say if this MCT was graded but I would have thought that if it was in a lymph node it would be metastatic and therefore a high grade MCT. The cat is still alive and well 15 months later with its condition controlled purely by diet. I may be proved wrong yet but I think this was a case of a technician misinterpreting inflammatory mast cells and drawing the wrong conclusion and it could have resulted in costly, unecessary treatment

Finally, from what I've been advised, Mastinib is no more expensive than some of the cytotoxic drugs already available to us like asparaginase for example and the ease of administration and low incidence of serious side-effects should make it an agent of first choice for mast cell tumours and as an adjunct in others. The results in humans in other tumours is already established and no doubt more TKIs will be developed as 'designer' target treatments for many more specific cancers in the near future. Exciting prospects.

Re: Metacam for malignant melanoma?

Rob Foale — Tue, 06 Jul 2010 00:14:20 GMT

Hi Trevor,

Well the histo looks pretty clear cut so I think it is delightfully difficult to explain the response you report! The continuing presence of the CNS signs obviously raises the possibility of continuing tumour disease being present, although the timeframe of this dog surviving is a little longer than I would expect now without there being significant disease progresion - long may this last, obviously.

Kate, yes meloxicam and piroxicam have been suggested as treatments for lingual SCC in cats and I have used meloxicam in the past but usually to try to offer some form of analgesia for short-term palliation. It is again difficult to explain the response you report, but as you are probably aware there is a huge body of literature in human medicine showing that COX-2 has roles in cell division, apoptosis, protein production, angiogenesis to name but a few and COX-2 anatgs do seem to help to some degree in some cases/tumour types, notably TCC in dogs and colo-rectal ACA in people. What confuses the picture more than a little is the fact that piroxicam is not COX-2 selective! However, on this basis I usually talk to clients owning dogs with OSA, anal sac ACA and other carcinomas in particular that there is little to loose by adding in meloxicam to their treatment regime as long as the concurrent chemotherapy isn't likely to be nephrotoxic (which obvously it often may be). Other treatments for lingual SCC that may be useful is photodynamic therapy and also bisphosphonate treatment, but this is a bad disease that very rarely ends well

WRT Martin's post concerning tyrosine kinase inhibitors, I am a big fan of these and think we will be using masitinib and its like more and more in the coming years in a variety of different tumour types (probably in combination with more traditional cytotoxic medications), which will hopefully result in a lowering of the cost which is currently sadly prohibitive for many clients. Interestingly, masitinib is probably efficaceous in MM so may be an option (off licence) for this disease Trevor in the future for some reason a dog canot be referred to an oncologist for xenogenic vaccination treatment.

Rob

Re: Metacam for malignant melanoma?

Julian Earl — Mon, 05 Jul 2010 23:13:24 GMT

Hasn't there been some work to show that piroxicam is effective against certain types of human neoplasia? Mammary tumours, possibly?

Also, if these histopathology results are accurate (and why wouldn't they be?) what does it say about intractable cases that receive homoeopathy?

Re: Metacam for malignant melanoma?

Trevor Turner — Mon, 05 Jul 2010 19:18:22 GMT

Here is the histo. Its quite succinct so I assumed there was little room for mistakes with the diagnosis.

FINN lab report, ref 09055857.
·Diagnosis Malignant Melanoma and Chronic stomatitis
Prognosis Guarded

Hlstopathology Report
3 tissues submitted (wedges), 3 sections examined.

LARGE
The Inflltratlve, submucosal mass consists of tightly packed groups of polygonal cells with faintly pigmented cytoplasm. These exhibit large nuclei and prominent nucleoli. There is a high mitotic rate (>30 per ten 40x fields).

Diagnosis: Malignant melanoma.

Comment:
Melanomas are common canine neoplasms, accounting for the many oral and digital tumours and 9 to 20% of all skin tumours. Behaviour of melanoma is variable, depending on location. Those occurring on the skin tend to be benign, whereas oral and digital tumours frequently malignant.
Oral melanoma Is an aggressive malignancy. Both recurrence and metastasis are common. Dogs with oral tumours < 2 cm have significantly prolonged survival intervals compared to those with larger masses. The prognosis for recurrent tumours Is less favourable than for primary tumours that can be controlled locally.

SMALL (x2)
Both samples are similar. The epithelium is hyperplastic. The fibrotic submucosa has deep, perivascular and Interstitial Infiltrates of lymphocytes and plasma cells. There are fewer neutrophlls, macrophages and eoslnophlls

Diagnosis: Chronic stomatitis.

Comment:
Both samples exhibit chronic, deep Inflammation. Chronic Infection, previous Injury and recurrent Irritation are potential contributing factors. A deep foreign body reaction is not ruled out There is no evidence of neoplasia.

Re: Metacam for malignant melanoma?

Martin Atkinson — Mon, 05 Jul 2010 17:20:52 GMT

Some of these cases do make me question histology results - like the castrated dog I had with an abdominal mass which came back as a testicular tumour (and yes before anyone says it: it had been cryptorchid and yes I personally had removed both balls some time before). However I recently was beamed up and saw the future (well at least I went to a lecture on tyrosine kinase inhibitors by Jerry Poulton of NDSR, notably Mastinib) and have been excited and inspired by how this class of drugs will change the way we treat cancer. Where is this leading? Well, part of the way Mastinib works against other tumours other than mast cell tumours is because apparently mast cells are involved in the inflammatory pathways which are involved when tumours metastasise and if you suppress the mast cells this reduces their role in mediating this process. Back 2 steps and I wonder if NSAIDs have a comparable role. Just a thought.

Re: Metacam for malignant melanoma?

Kate Richardson — Mon, 05 Jul 2010 14:22:49 GMT

Oh and I did get the histology reviewed!

Re: Metacam for malignant melanoma?

Kate Richardson — Mon, 05 Jul 2010 13:43:59 GMT

On a similar but slightly different note, I have a cat, Brian, who I diagnosed with an oral squamous cell carcinoma about 3 years ago on his tongue. His owner, a very dedicated lady, was keen to do as much as possible, so I debulked the tumour as best as possible, and started him on meloxicam. In the first 6 months the tumour was still evident and appeared to be regrowing, but gradually after that it started to resolve (clinically) to the point where no obvious tumour was visible to the naked eye. A further 6 months later we started to wean him off the meloxicam but started to see a small ulcerated area regrowing so went back onto the full dose. 3 years later still no clinical signs of tumour regrowth. I know there is evidence for Cox 2 suppression on some of these tumours but I'd be interested to know if many other people have had this experience. Incidentally this cat also has concurrent hyperthyroidism, renal insufficiency and secondary hypertension and hypokalaemia, all medically managed, and Brian is now 18! Amazing cat and amazing owner!

Re: Metacam for malignant melanoma?

Rob Foale — Mon, 05 Jul 2010 11:09:39 GMT

Dear Trevor,

Sounds like an interesting case! There is quite a considerable volume of literature in human medicine showing that COX-2 expression is high in human malignant melanoma but no work has managed to show that antagonising it's expression reduces the rate of cell proliferation in cell culture to my knowledge in either human or veterinary medicine. COX-2 may have some role in aiding/promoting angiogenesis for MM but I am not aware of any reports of COX-2 antagonists working at all in the clinical situation either. WRT the vaccination, Rob you are correct there is now one available but it can only be sourced through Specialists I'm afraid. The vaccine is a xenogenic DNA vaccine which stimulates the production of anti-tyrosinase antibodies and it is a safe and efficaceous treatment for MM in the dog that generates signiticantly longer survival times in treated patients compared to controls, but it is not a cure for most.

Therefore, I think either your dog is really lucky and it has experienced a spontaneous remission (MM can do strange things at times but I've not seen this!) or, without wishing to appear rude, the histo needs reviewing.

Hope this is useful?

Best wishes,

Rob Foale

Re: Metacam for malignant melanoma?

Rob Davis — Mon, 05 Jul 2010 10:38:57 GMT

I know the AHT (and I think others) have been trialing a melanoma vaccine (? stimulates immune response against melanocytes) with good success. Is it possible that the dog's own immune system has mounted such a response?

PS Never seen anything like this, and I'm neither an immunologist nor an oncologist, so happy to be ridiculed!

Re: Metacam for malignant melanoma?

Evelyn Barbour-Hill — Sat, 03 Jul 2010 21:22:24 GMT

Very interesting!

[quote user="Trevor Turner"]So:- Are malignant melanoma Cox2 senstive?[/quote]

Not as far as I know (but I can't recall seeing anything about it, so maybe no-one has ever tried).

[quote user="Trevor Turner"]Or is this spontanous remission?[/quote]

Always possible I guess but unheard-of.

[quote user="Trevor Turner"]Or a mis-diagnosis? [/quote]

Always possible if unlikely.

[quote user="Trevor Turner"] Is there anything else I can throw into the mix the help Freya out?[/quote]

See if you can talk to Susan North at VRCC