Nightmare lymphoma case

Re: Nightmare lymphoma case

Gerry Polton — Thu, 09 Oct 2014 08:28:08 GMT

having got the response you have, I suspect there is nothing more efficacious than the lomustine and prednisolone. You give the answer yourself in your question: just press on with the lomustine and prednisolone, so long as the dog makes a full recovery from the pancreatitis. Do be cautious when giving the next dose of treatment and do consider withdrawing prednisolone if you are suspicious that this is not helping matters.

This is a very difficult case, Kara.

Gerry

Re: Nightmare lymphoma case

Kara Gibson — Thu, 09 Oct 2014 02:43:24 GMT

The nightmare continues....

Started this dog on the above protocol having checked his liver enzymes nad CBC before commenicng chemotherapy. He presented 6d after the L-asparaginase and lomustine off his food, pyrexic and with some liquid diarrhoea. Actually his WBCs remain fine but after a bit of investigation it turns out he had developed pancreatitis! Of course he did, he is after all a GSD.

He seems to be responding to treatment and his cPL snap test yesterday came up negative but his owner is now questioning the next step for chemotherapy (she will really not accept that this dog is not doing well despite many long discussions with several of us). His LNs did respond quite nicely to the first load of treatment but we obviously cannot use L-asparaginase again. We would be inclined to just use lomustine and prednisolone but his owner is keen for us to check if there is anything potentially more efficacious we could use.

We are more than happy to accept if there aren't any more suggestions, at least we can go back to the owner having tried!

Re: Nightmare lymphoma case

Braden Collins — Thu, 11 Sep 2014 04:40:25 GMT

What a tough case.

When I'm administering chemo drugs I will place the catheter once I am ready to administer the drug, and remove it as soon as I am finished. If my catheter placement isn't perfect it doesn't get the drug in that vein and I move on to another leg. All owners are told at the start of any protocol that if I'm not 100% happy with catheter placement the dog doesn't get the drug and they may need to come back another day if I run out of suitable veins (hasn't happened yet).

I don't think it matters which leg you use if you do continue doxorubicin so long as your catheter placement is perfect - after all, extravasation again will make the leg slough and it no longer has the spare leg. I will happily give doxorubicin into a hind leg if needed, but it takes a bit more skill to get the catheter right. I will sedate if needed to assist easy catheter placement in a fractious dog.

I would guess the leak around the catheter was present at the time of injection, not just in the following 2 hours so I would look at your protocols for ensuring the catheter placement is correct and there is no leaking, such as flushing, exposing the catheter at the time of administration so you can see if there is evidence of extravasation, etc. I won't even let another vet place my catheters for chemo, I will always do it myself as it falls back to me if things go wrong.

I think Doxorubicin is too much of a useful drug to drop based on fear of what might go wrong with a case like this.

Re: Nightmare lymphoma case

Martin Atkinson — Wed, 10 Sep 2014 19:32:47 GMT

Not going to comment on any welfare issues here. But I had a dog which got horrendous haemorrhagic diarrhoea following doxorubicin so the owner elected to stop it. It was on a 27 week modified Madison protocol with l-Asparaginase. It went to the end of the protocol without any more doxo (by which time we were really struggling to find a vein anywhere) and stayed on preds for another 18 months whereupon I ceased treatment. It is still alive and in remission over 4 years later! I (and Gerry!) would consider that a cure.

Re: Nightmare lymphoma case

Hannah Wynne Richards — Wed, 10 Sep 2014 15:51:48 GMT

Kara You're the one treating this case - I haven't seen it - but it does sound horrendous. You don't have a legal right to forcibly euthanase (incidentally, this is one where I'd be prepared to use the term euthanasia - as opposed to contract killing) - you do have a right to say, "I think that continuing to allow this animal to live constitutes a criminal offence of causing unnecessary suffering. I think the RSPCA should be involved."

Only those treating the animal can know whether it really is this bad with this animal

Wynne

Re: Nightmare lymphoma case

Anthony Todd — Wed, 10 Sep 2014 12:04:56 GMT

[quote user="Kara Gibson"]doxorubicin dose his leg[/quote]

I wonder why doxorubicin causes sloughs? Is it pH, if so it may pay to find out if it is acid or alkaline and use a flushing solution to help correct the pH.

Back in the day we used plain procaine [pH <7, or >7, [can't remember, but it was not 7ish], and no adrenaline with saline which worked well after the inevitable thio extravasation 'cos thio is, I think, highly acidic.

Remember those black cats with the white dot on the I/V site.....

I think Hartmans is not pH 7, so if that makes it nearer pH 7 you may avoid an amputation.

Of course, it may be nothing to do with pH at all ,but it's worth a thought.

Re: Nightmare lymphoma case

Kara Gibson — Wed, 10 Sep 2014 11:57:58 GMT

Thanks Gerry, very helpful advice as always.

Wynne, I absolutely agree with you on this one. When we realised we couldn't save his leg we pushed for PTS, but his owners absolutely refused - we tried drains, hospitalisation etc but it got to a point where the muscle had necrosed and we had to amputate given that his owners would not even contemplate PTS. We all feel this was not in the dogs best interests but what could we do at that point, we can't forcibly euthanase him?

Re: Nightmare lymphoma case

Hannah Wynne Richards — Wed, 10 Sep 2014 11:34:19 GMT

I have to ask the obvious question:

Is the welfare of the animal,or the wishes of the owner the 1y consideration in this case?

Wynne

Re: Nightmare lymphoma case

Gerry Polton — Wed, 10 Sep 2014 11:15:58 GMT

OMG! That certainly is a nightmare case. As a complete aside, if you have any photos of the case that you would not mind me using in lectures I would be eternally grateful.

For high grade lymphoma the best predominantly oral protocol is the combination of L-asparaginase and lomustine (+/- prednisolone). This is my preferred rescue treatment for dogs that have come out of remission and failed CHOP chemotherapy. The reference that you want to look up if you are interested in Saba et al, JVIM 2007: see abstract copied below. However, my experience is that the treatment in question works best in cases that are truly resistant to CHOP chemotherapy. It is interesting that other oncologists have reported the use of a similar protocol as a first line therapy and the results are consistently poorer than CHOP as a first line treatment. The alternative that would be worthy of consideration and would allow you to continue CHOP chemotherapy or other injectable protocols with greater confidence would be to implant a vascular port. That might be a better option in this case.

Gerry

Combination Chemotherapy with L-Asparaginase, Lomustine, and

Prednisone for Relapsed or Refractory Canine Lymphoma

Corey F. Saba, Douglas H. Thamm, and David M. Vail

Background:

Canine lymphoma (LSA) is responsive to initial treatment, however, it then becomes resistant to drugs in the

initial protocol. New rescue protocols are needed.

Hypothesis:

A combination of L-asparaginase, lomustine, and prednisone will be well tolerated and efficacious as a rescue

therapy for dogs with LSA.

Animals:

Thirty-one client owned dogs with cytologically confirmed multicentric LSA who were refractory or whose disease

had relapsed after a CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-based chemotherapy protocol.

Methods:

Prospective clinical trial. Lomustine (target dose, 70 mg/m2

) was administered orally at 3-week intervals for a total

of 5 doses or until disease progression. L-asparaginase (400 U/kg) was administered subcutaneously concurrently with the

first 2 lomustine treatments. Prednisone was administered at a tapering dose for the duration of the protocol.

Results:

Overall response rate for dogs treated with this protocol was 87% (27/31), with 52% (16/31) of dogs achieving

a complete response. Median time to response was 21 days. Median time to progression was 63 days (111 days for dogs

achieving a complete response and 42 days for dogs achieving a partial response). There were no significant differences in

response rates and times to progression between dogs who had received L-asparaginase before beginning this rescue protocol

and those who had not. Toxicoses were mild and self-limiting in 29 of 31 cases.

Conclusions and Clinical Importance:

This is a well-tolerated rescue therapy for relapsing LSA in dogs. Response rates and

remission durations compare favorably to other rescue protocols. Therefore, this protocol is a viable rescue option.

Key words:

Asparagine; CCNU; Dogs; Lymphosarcoma; Rescue protocol.