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Thread: Has anyone treated with 9-cis Retinoic Acid?

  1. #1
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    Default Has anyone treated with 9-cis Retinoic Acid?

    There is a study by Dr. Victor Castillo at the University of Buenos Aires veterinary school that used a 180 day treatment and showed tumor shrinkage through MRI. Does anyone know of this treatment being done in the US? The cost is similar to Vetoryl. The study indicates remission and a cure? Please comment.

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    Default Link to Published Research utilizing 9-cis Retinoic Acid


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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    Hello and welcome! We have had a bit of discussion here previously about retinoic acid and this particular 2006 study. However, none recently. This leads me to believe that the "question marks" that are noted in the thread below must remain. But if you can find any newer info, that would be great. Here's the related thread:

    http://www.k9cushings.com/forum/showthread.php?t=2000

    Do you have a dog who is currently being treated for Cushing's?

    Marianne

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    Thank you for the thread link. I've directly contacted Dr. Castillo and he told me that they have been treating Cushings for nearly 10 years this way with success. He estimates the cost to be $40 to $90 for 30 capsules at 14mg (the dosage required for a 7kg dog). I am waiting for the pharmacy contact information from him.
    Yes, I do have a 8 1/2 year old 15lb intact male Cairn Terrier currently being treated with Trilostane along with Homeopathics and a raw low purine diet. We're on the 2nd stim test from a whopping 70 his first stim prior to treatment, down to 15 with 5mg 2X. My vet suggested liquid form Trilostane to raise the dosage to 7.5mg 2X. He has definitely improved. His thirst changed in just a few days. Less panting now that he's been on the Vetoryl for a total of 4-weeks. I am thinking about trying the Retinoic Acid once more of his symptoms lessen and his stim gets below 5. It's been slow getting replies from Dr. Castillo but he does answer eventually.

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    That's very interesting that you've been able to contact Dr. Castillo directly. It will also be interesting to get the pharmacy info, since it appeared that obtaining the drug at an affordable price was a big issue here in the U.S. I have just now emailed an expert veterinary endocrinologist here in the U.S., requesting an update re: current use of retinoic acid here. He usually answers very promptly, and I'll definitely post any related info here as soon as I receive it.

    Marianne

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    I went to read the abstract of the article and I am by no means an expert or even anything close Yet, it left me with some questions and I did try to look for them on the internet but couldn't find anything.

    In the abstract they mention the trial was done with 22 dogs receiving retinoid acid and 20 dogs receiving ketoconazole as treatment. To me, this is strange, since ketoconazole isn't the most effective treatment in canine cushings. In my layman mind, I would think "Yeah right, compare a possible new treatment to a not very effective treatment...and chances are the outcome will be beneficial for the new treatment" So I would like to know how the retinoic acid compares to treatment with Vetoryl for example...yet, I cannot find any study on this. In fact, I cannot find any other studies on treating canine cushings with retinoic acid after this one from the abstract, which was 10 years ago in 2006. This too, seems strange to me. I did find a much more recent study of a trial with human cushings patients and retinoic acid. https://www.hindawi.com/journals/ije/2016/8173182/ In that article there is no mention either of trials in canines from a later date then 2006. They only refer to the 2006 trial. And humans and canines are different of course so you cannot compare those results one on one but eventhough it does seem beneficial to certain human cushings patients, it is not to all. So there still is a long way to go

    I am notoriously curious, I appologize...but could you explain why you would want to change the Trilostane treatment (who seems to be working well from what you write) for the retinoic acid? I couldn't find anything indicating that treatment with retinoic acid would/could cure cushings. In fact, as far as I understood it, the dogs were treated for 6 months (180 days) but what happened after that. Was treatment stopped all together? It doesn't say in the abstract...but perhaps you have the full article available and there it said maybe more?

    Anyway, to me personally, it just gave me more questions then that it seemed to be a lasting solution to treat canine cushings disease.

    Love a good exchange of ideas and thoughts...

    Saskia

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    OK, I've already heard back from Dr. David Bruyette who is the medical director of VCA Animal Hospital in West Los Angeles, has been instrumental in pioneering surgery for canine pituitary macrotumors at UCLA, has been a consultant to Dechra re: Vetoryl, and is also conducting ongoing clinical research himself. Apparently the cost of obtaining retinoic acid in the U.S. remains prohibitive and that has cast a pall on further research here. This is what he wrote to me:

    No one has really advanced the therapy very far given the costs and the availability of paseriotide and mifepristone which recently became approved for use in humans.
    I am not familiar with these other two chemicals, so I need to read more about them. But apparently cost is an issue with them as well, since when I asked him further about them, Dr. Bruyette said they do work in dogs but are also very expensive.

    It does seem a shame if all these chemical alternatives might otherwise present a safe and therapeutic treatment alternative, if it were not for expense. Anyway, I guess this explains why the research has not yet gained additional traction in terms of veterinary use.

    Marianne

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    Thank you for your comments regarding the study and I appreciate the exchange of thoughts. Here are my concerns: Trilostane is a perpetual treatment of symptoms, manually down-regulating cortisol. Cortisol is also beneficial and necessary. This may contribute to the hind leg weakness my dog is showing. It concerns me that the drug is very potent and dosage must be closely monitored and precisely dosed especially for a 7kg dog. Life expectancy for Trilostane is only a median of 540 days. My dog is only 8 1/2 years old, he should do better than that I hope.

    If the Retinoic Acid performs as stated in the paper it could be a cure. It states there were no negative side effects. There are several before and after MRI images showing visible shrinkage of Pituitary Masses. At best, in optimism the paper in summary says: "some 6–12 months after completion of the trial and cessation of treatment, none of the dogs treated with retinoic acid has shown evidence of recurrence of Cushing’s disease."

    Mitchell

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    Unfortunately no reply from Dr. Castillo yet with the pharmacy contact information. I will post once I receive the information. Thank you for asking Dr. Bruyette about this.

    On another note, would you know Dr. Bruyette's thoughts regarding splitting dosages since Vetoryl peaks at 4-6 hours? I contacted Dechra and although in their handbook there are references to studies where splitting dosage was done, according to the person I spoke with 'do not officially recommend it'. The reference studies do state that it lessened the side effects with more consistent UCR measurements.

    Mitchell

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    Default Re: Has anyone treated with 9-cis Retinoic Acid?

    Yes, we do know Dr. Bruyette's thoughts about this . He was actually a member here for a short time, and here's a reply that he posted to that very question. It's been a couple of years since he visited us here, but I believe his current approach remains consistent.

    With regards to once vs twice a day dosing if we look at all the studies throughout the world you will see that about 80% of dogs will feel better with once daily dosing. One huge advantage of once daily dosing is owner compliance which goes up substantially when owners only have to dose once a day. While twice a day dosing may result in a lower amount of trilostane being used per day it will require closer monitoring as the ACTH stimulation tests tend to be lower so we have to look for both hypocortisolemia and electrolyte abnormalities.
    The question of once vs. twice daily dosing has consistently remained a topic of debate among clinicians throughout the years, and different folks have different perspectives and preferences. In my own mind, the research remains somewhat equivocal in terms of lessening ill effects. It seems to be the case that certain side effects may be lessened by the lower total daily dose that can be associated with twice daily dosing. Also, some clinicians speculate that longterm systemic damage may be lessened when cortisol levels are kept consistently lowered throughout the duration of each day. However, as Dr. Bruyette notes, twice daily dosing may carry an increased risk of driving cortisol levels too low, which to me is actually the most worrisome potential side effect of all.

    Given the fact that every dog metabolizes the drug a bit differently, my personal belief is that some dogs will feel better on once daily dosing (allowing their cortisol to rise somewhat throughout the course of 24 hours), and others will do better with cortisol levels that remain more consistently flat. If I were starting out all over again, though, unless I had a diabetic dog for whom twice daily dosing is generally always recommended, I think I'd ask to start off with one dose each morning and I would only shift to twice daily dosing if symptoms rebounded again later in the day. In my own daily life and schedule, it is just much easier for me to remain consistent with a single dose each morning, especially since trilostane needs to be administered along with a full meal in order to be metabolized properly. I see that you are dosing twice daily, however, and if that regimen seems to be working well for you, there are certainly many clinicians who favor that approach.

    Marianne

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