Holly's Magic Mushrooms, Part 2

Holly's Magic Mushrooms, Part 1

 

Although at one time I was on low doses of the chemotherapy drug methotrexate for my RA, I have been lucky in that no one close to me has had chemotherapy for cancer treatment.  Talk about cognitive dissonance!  Purposefully injecting the body with something so toxic just seems insane!   On the other hand, to do nothing felt as if I was giving up on Holly.  Low dose oral (metronomic) chemotherapy sounded like a compromise.

 

I really liked the oncologist at the university vet clinic.  She sat on the floor with us and handed out treats and discussed our options extensively.  Here are some of the numbers she gave me; 93-95% of pets do not have any significant side effects from doxorubicin treatment; the most common side effects of diarrhea, nausea, vomiting and low white cell count occur in only 5-7%, are usually mild, and are prophylactically treated with medication.  She emphasized that her goal was not just to extend Holly’s life, but also that Holly have a good quality of life.  She reiterated that the best standard of care was doxorubicin chemotherapy (again, limited to 5 treatments due to heart toxicity), followed by metronomic chemotherapy.  She also emphasized that she would support my decision, whatever I chose to do, including deciding to forego treatment.  She also did some blood work and Holly was still slightly anemic, although not, in her opinion, low enough to preclude a chemotherapy treatment.

 

I went to our appointment determined to use metronomic chemotherapy.  But after talking with the oncologist, I wasn't so sure of my decision; I went out to the car and called my mom, I walked around trying to think, I went into the clinic and got a cup of coffee.  While I was in the waiting room, the oncologist brought a print out to me of this University of Pennsylvania press release .  After debating for some time, I decided to go with doxorubicin treatment and see how things went; I felt so uncomfortable with my decision, but I wanted to give Holly the best chance.

 

As I had taken a ½ day of vacation for our appointment and we were coming into a holiday weekend where I could be home with Holly and monitor her (please note that you do NOT want to have chemotherapy treatment right before a holiday weekend, as will become evident), we went ahead with a doxorubicin infusion that afternoon (Wednesday, August 31).  Holly received 15.5 mg doxorubicin by IV and she was also given an injection of the anti-nausea medication Cerenia (16 mg).  We were sent home with a 4 pack of Cerenia (60 mg) to be given once a day (starting the following day) and metronidazole (250 mg) (aka Flagyl) for diarrhea, also to be started the following day.  I was also instructed to get a rectal thermometer and if Holly acted sick/her temperature went to 103^o or greater, to take her immediately to my vet/an emergency vet, as any infection could be life threatening.  I set an appointment for the following Wednesday for a follow-up to check Holly’s white cell count.

 

Holly was perfectly normal that evening.  I had more than a few moments of alarm when I fully read the handout; yikes! guess I should have asked about any special precautions I should take since I am on an immunosuppressant, but it never occurred to me. . . Holly ate as normal the next morning, and took her mid-day snack, but that evening she gave me the side-eye when I put her dinner down, and I ended up hand feeding her.  The next morning (Friday) she wouldn’t take her food even by hand.  By the evening, I realized that she was not drinking either.  The following day I began to offer Holly small portions of a variety of bland foods, along with broth, but she continued to refuse all food and liquids.   I also began checking her temperature a couple of times a day; it remained normal. 

 

I called the emergency number the university clinic had given me around 6 am the following day (Sunday).  The emergency vet on-call suggested a few more foods to tempt Holly with, and asked if I could wait until 8 am for her to call the on-call oncologist, as it was both a Sunday and a holiday weekend.  I received a call back from the emergency vet (not the on-call oncologist) around 9 am and was told that if Holly continued to refuse food and water I should take her to an emergency clinic on Monday (remember, holiday weekend) and that she should be given subQ fluids and the drug mirtazapine to stimulate her appetite.  I continued to offer Holly small portions of both bland and stinky foods, as well as broth, water and ice chips.  I tried using a syringe to get water or broth down her, but she just let the fluid trickle back out of her mouth.  The last time she had anything to drink was, at best, early Friday morning.

 

Instead of waiting for Monday morning, we went to the emergency vet late afternoon Sunday.  Holly was given a relatively small amount of subQ fluids (400 ml) and a prescription of mirtazapine (15 mg).  I gave her the mirtazapine as soon as we got home.  About an hour later, Holly began having explosive, liquid diarrhea, which continued through Monday (Labor Day). 

 

I called the university clinic first thing Tuesday morning and requested and immediate appointment.  Holly’s weight had dropped by 2 pounds in six days and blood work showed her to be slightly more anemic than at our previous appointment (now down to 31%), decreased neutrophils (as expected), and elevated protein levels consistent with dehydration.  They gave Holly 900 mls of subQ fluids, and another package of cerenia (which I did not end up using) and additional metronidazole.  The fluids helped A LOT; Holly began drinking voluntarily when we got home, and ate a scrambled egg that evening; the following days she continued to eat small portions of scrambled egg as well as chicken.  Although she no longer had urgent diarrhea, she continued to have loose stools.

 

I took Holly in to our regular vet that Friday to recheck her anemia and neutrophils; both had come up to borderline normal values.  I also brought a copy of the University of Pennsylvania press release (see link above) for my vet, and let him know that I was going to use this as treatment for Holly’s hemangiosarcoma going forward – no more chemo for Holly.

 

I’m-Yunity is a supplement derived from Coriolus versicolor (turkey tail mushroom or yun-zhi).  Since the full Latin name is a mouthful, I've taken to calling this supplement Holly's Magic Mushrooms :)  Specifically, the active agent is a polysaccharopeptide (PSP), which has been shown to have in vitro antitumor activities, without having inhibitory effects on normal cells.  An isolate derived from Coriolus versicolor, known as polysaccharide-K (PSK or PSP), is used in some countries as a therapy for patients undergoing chemotherapy for cancer; it is intended to counteract the negative effect that many chemotherapeutic agents have on the immune system. In addition, PSP in China and PSK in Japan, are government registered anticancer drugs, commonly used as a supplement to surgery, radiation and chemotherapy.  Here is a link to a 2012 research paper using I’m-Yunity as treatment of hemangiosarcoma in dogs.  To quote from the results “While there was no statistically significant difference in the survival curves amongst the 3 dose groups, the two highest dose groups had median survival times longer than the longest median survival time reported in the literature to date, which is 86 days, as compared to 117 days in dogs receiving 50 mg/kg/day I’m-Yunity and 199 days in dogs receiving 100 mg/kg/day.”

 

Our fist order of I’m-Yunity arrived on Thursday, September 15.  Out of an abundance of caution, I gave Holly ½ dose that evening and the following morning, and then upped her to a full dose (100 mg/kg/day), which I have continued to this day. 

 

Some changes I have noted following Holly’s splenectomy and doxorubicin treatment.  Holly’s digestion continues to be ‘delicate’; she still occasionally has loose stool, and I only recently have been able to get her to reliably eat her previous diet.  I continue to give her small portions of scrambled egg or chicken next to her portion of Honest Kitchen food (see link in side bar); it seems to stimulate her appetite to start each meal with one of these preferred foods.  I have noticed that giving her metronidazole seems to negatively affect her appetite, so I don’t automatically give it when she has an isolated loose stool.  Holly’s hearing has become really poor.  She seemed to have some slight age related hearing loss prior to chemo, but her hearing is pretty bad at this point.  Following doxorubicin treatment, Holly stumbles and trips quite a bit; she has fallen right on her face several times.  Holly’s arthritis is considerably worse, however, I have not been able to get her back on carprofen at this point.  Every time I have given her a dose she has diarrhea, so I am using Gabapentin alone to treat her arthritis (she only inconsistently will take the chewable joint supplement I use). 

 

Other than the above noted issues, Holly seems to feel pretty good.  She’s back to her sassy, saucy self most of the time; her 13^th birthday is less than a month away.  I will try to update regularly with how Holly is doing with her magic mushrooms. . .

Holly's Magic Mushrooms, Part 1

'Yeah, I've Got That' will be taking a detour for the foreseeable future.  I will briefly note that I have been at goal weight (actually 5 lbs below my original goal of 125) of 119-120 since January of this year and both my RA and IBS are 'stable'; I continue to follow a Wahls Paleo Plus/primal diet and I continue mountain bike and weight lift. 

As I was desperate for information in the days following my dog's diagnosis with hemangiosarcoma, I want to tell our story so that other dog owners can hopefully use our experience in their decision making process in regards to treatment.  This is OUR experience - your mileage may vary.

 

 

Meet Holly.  At one time she trained/showed in Agility, Tracking, Obedience and Rally.  She's been 'retired' to hiking partner extraordinaire (along with my other dog, Mikey) for many, many years.

           Yes, she looked a lot like a stuffed toy when she was a puppy!

  

 

 

 On August 11 Holly was a 'normal' 12 ½ year old Cardigan Welsh Corgi with hip dysplasia and arthritis; in fact she and I played some serious tug that evening while I played fetch with Mikey, since it was too hot out for our normal post-work walk.  The morning of August 12, it appeared she had pooped on the floor in the bedroom overnight (although it could have been Mikey), she was also very listless and refused her breakfast (a big red flag in our house!).  As I was working from home that day, I sat on the couch with her working on my laptop until my vet opened for the day.  I noticed that every few minutes her abdomen was contracting very hard and her respiration was elevated.  This continued until we left for our appointment.

 

Following a physical exam, my vet gave Holly an abdominal x-ray and blood work.  The x-ray showed a mass in the location of her spleen and the blood work showed elevated platelets and slight anemia.  Our vet directed us immediately to a specialty clinic, where an abdominal ultrasound confirmed a tumor off the spleen which had ruptured, causing internal bleeding.  While my vet had called ahead and spoken with the oncologist on staff, they left before we got there and I met with an emergency vet, who explained the findings from the ultrasound and x-ray.  She told me the likely diagnosis was hemangiosarcoma and told me what my immediate options were (do nothing and see if the bleeding resolved, euthanize Holly, or immediate surgery to remove her spleen). Additional x-rays showed that her lungs and heart were clear of tumors, so an emergency splenectomy was scheduled for that afternoon.  During surgery, the surgeon identified suspicious lesions on her liver, which she biopsied.  The liver biopsy was benign, but the biopsy of the spleen (received the following week) confirmed a diagnosis of splenic hemagiosarcoma. 

 

I was able to bring Holly home 24 hours after her surgery.  She was obviously in quite a bit of pain the first few of days, but the pain seemed to be well managed with Gabapentin, tramadol and carprofen (I was given enough to last through 6 days, although lower doses of carprofen and Gabapentin were already part of her normal support for hip dysplasia/arthritis).  I started her with bland foods (scrambled eggs, bone broth and chicken) and her appetite picked up quickly over the next couple of days.  Once she was able to eat her normal diet, I continued with the bone broth and extra protein to aid in healing.  Her incision (from approximately a few inches below her sternum to a couple inches from her genitals) was closed with staples.  I examined the incision at least twice daily.  The first day home there was rain, and at her height she did get a little moisture from the grass/ground on her tummy when we went outside for bathroom breaks, which I gently blotted off with paper towels.  I had scheduled to have Holly’s staples removed by my regular vet on the 10^th day after surgery; however her incision looked red and swollen to me the morning of the 9^th day, so I took her in to my vet.  Luckily the redness and slight swelling was due to irritation from the metal (Holly’s tummy sags slightly due to age, with a loose fold of skin down the middle, which caused the staples to rub this area).  My vet removed her staples and cleaned her tummy of lingering scabs and everything looked much better.

 

In my case, the surgeon was the individual who called with the biopsy results.  While both my vet and the emergency vet at the specialty clinic gave me an outline of what a diagnosis of hemangiosarcoma means and that chemotherapy is the standard of care following surgery, I had not yet spoken with the oncologist on staff at the specialty clinic, and the surgeon didn't discuss treatment with me. The time I’d spent online researching hemangiosarcoma in the days between surgery and the call to confirm diagnosis was not very encouraging, to say the least, and left me with a lot of questions in regards to post-surgery options.  The bottom line; hemangiosarcoma is not ‘curable’; it is highly aggressive and metastatic.  Treatment is geared toward extending life span.  With surgery alone survival is typically 2 to 4 months.  Chemotherapy following surgery may extend survival by another 2 to 4 months.   Due to the aggressive nature of hemangiosarcoma, I knew that prompt treatment (if I chose to treat) following Holly’s recovery from surgery was crucial.

 

A call to the specialty clinic where Holly had her surgery was frustrating; they simply expected me to make an appointment and show up with Holly for her first chemo.  I requested a call-back from the oncologist to discuss options.  My time spent on the internet had led me to believe that the standard treatment with doxorubicin (adriamycin) might not be a good choice for Holly.  If I was going to treat at all, I thought that the low dose oral (also called metronomic) chemotherapy might be a better option.  After three days without a call back, and already a bit concerned that I did not meet with the oncologist the day of Holly’s surgery (when my vet had called ahead and the oncologist said they would meet with me) and when I was called by the surgeon rather than the oncologist with the biopsy results, I decided to try another clinic.  I made an appointment for August 31 at a local satellite clinic for a Missouri state university school of veterinary medicine with an oncologist on staff (among other specialists).  My vet was familiar with this clinic, although only with their radiology department.  At the time I made my appointment, I specifically asked if they offered metronomic chemotherapy.

 

I want to give an overview of both doxorubicin and metronomic chemotherapies; the below is a primarily from the handouts I was given at the university clinic. 

 

Doxorubicin (adriamycin) is currently the standard chemotherapy treatment for dogs with hemangiosarcoma.  It is given via IV infusion by a veterinarian and dosage is based on the estimated body surface area.  Please note that calculation for body surface area (BSA) can be problematic for smaller dogs, as body length is not part of the calculation. (http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.1998.tb02121.x/pdf )  Typically, doxorubicin dosing is every 3 weeks for a total of 5 treatments.  Side effects include:  1) nausea, vomiting, diarrhea and loss of appetite, normally occurring within 2-5 days of dosing 2) low white cell counts, specifically neutrophils, with lowest counts occurring between 7-10 days of dosing 3) severe tissue damage to the leg if a spill occurs from the catheter during infusion; tissue damage may be so extensive as to require amputation of the leg 4) heart failure; doxorubicin toxicity to the heart is dose dependent and limits treatment to total of 5 treatments; however pre-existing heart conditions may cause toxicity at lower dose exposures.  It is important to note that the dog’s feces and urine should be handled with gloves for up to 48 hours following treatment; this is of particular import for immunosuppressed or pregnant individuals.  UV light exposure (aka sunlight) denatures doxorubicin. Amusingly (to me) the handout I was given instructed both pregnant and immunosuppressed individuals to avoid contact with their pet for at least 72 hours after dosing.  So who, exactly, is supposed to care for the dog if you live alone (as I do) and you are taking an immunosuppressant drug (as I do)?  This was not something that was discussed by the oncologist, I found the information in the handout I was given, which I did not read in full until I arrived home after our appointment.

 

Metronomic chemotherapy is given orally and is administered at home.  It is a continuous dose (daily or every other day) combination therapy of low dose chemotherapy (commonly the drug cyclophosphamide), a non-steroidal anti-inflammatory (aka NSAID, such as carprofen) and an antibiotic (such as doxycycline).  Side effects from the chemotherapy drug include bone marrow suppression (and resulting low white cell count and/or anemia), gastrointestinal upset, and clinical symptoms of urinary tract infection (frequent urination, straining to urinate) without actually having bacteria in the urine.  NSAIDs can cause gastrointestinal upset and potential GI ulceration.  Antibiotics can cause gastrointestinal upset.  Because the drug is kept in the home and administered at home, extreme care should be taken in handling and storing the drug.  The same above suggestions regarding immunosuppressed/pregnant individuals apply.

 

Doxorubicin therapy is given at maximum tolerated doses, with the goal of killing the rapidly dividing cancer cells; it also kills or damages normal body cells that are rapidly dividing, such as GI tract cells and white blood cells.  This damage to normal cells is the reason there is a 3 week break in the treatment regimen, to allow these normal body cells to recover.  Metronomic chemotherapy is given at low doses and targets inhibition of tumor blood vessel cell growth. Tumor blood vessel cells are more active than normal blood vessel cells.  Both cyclophosphamide and NSAIDs have shown the ability to slow blood vessel cell growth.  Doxycycline has been shown to inhibit tumor cells’ ability to invade and grow in a new environment.

I'm working on Part 2, Holly's first doxorubicin treatment (on August 31), what happened and where we are now. . .