photo by Tami McKenna
David & Clondike at the 1999 GPCA National Specialty.
This article is an updated version of one written for the Great Pyrenees Club of America's Bulletin where it appeared in the July/August 1999 edition under the title "Another Year with Clondike."
It began one evening in May, 1998 with what was supposed to be a routine appointment to allow our regular vet to re-check Clondike's anal sacs. Before the visit was over, the vet was in tears--never a good sign!
I almost didn't mention the "funny" soft lump I had felt in the folds of Clondike's neck while brushing her that week. I expected to be told that it was some normal structure that I had never noticed before, like the time I rushed Clondike in to have a lump on her stomach checked, only to discover that she had a completely normal belly button!
The vet felt Clondike's neck and became really serious. She said anytime a dog has swollen lymph nodes you have to consider cancer as one possibility, and that she usually puts dogs on antibiotics for two weeks to see if the nodes go down before doing a biopsy. When I reminded her that Clondike was just completing a three-week course of antibiotics for the anal sac infection, she felt some more and said that, while the nodes didn't feel exactly like lymphoma patients she had diagnosed in the past, it was something we definitely needed to consider.
She asked if cancer were diagnosed, would we want to treat it? There were some new protocols that could offer a year or two of remission and since Clondike was 10 1/2 years old at the time, two years sounded pretty good. That pretty much dictated a nodectomy and tissue biopsy rather than a needle aspirate. Our vet said she had been getting about 50% inconclusive results from needle aspirates, plus oncologists prefer the tissue biopsy to help them determine the stage of the disease and determine the best course of treatment.
Clondike's surgery was scheduled for the next week with the clinic's best surgeon. She had no problem with the procedure, but did develop a huge goose egg at the incision site, a result of the body trying to fill the void with fluid. She looked like Dr. Frankenstein's dog and missed some therapy visits because we didn't want to scare the nursing home residents.
Nine days after the surgery we got a call that the biopsy was positive for lymphoma.
We Do Our Homework.
During the nearly two weeks between that first vet visit and the confirmation of the diagnosis, we had requested information on three Internet mailing lists. Janet Ingram (GPCA Rescue Chair at the time) saw my post and immediately mailed me a book entitled Managing the Veterinary Cancer Patient by Ogilvie and Moore. This 1995 text designed for general practice vets is pretty slow reading, but helped us understand chemotherapy and what it has to offer for canine lymphoma. It also emphasized the need to act quickly, as the average life expectancy of untreated dogs is only eight weeks.
We had received an excellent recommendation for a holistic vet who uses acupuncture and nutrition to help dogs battle cancer. With our general practice vet's blessing we called for an appointment to see if there were things we could do to help the chemotherapy work better. Unfortunately the holistic vet could not see us for a month, so that part of the treatment plan had to be put on hold.
Our vet had told us that with cancer you want the latest treatments, and that in our area there was a board certified veterinary oncologist who was doing some really innovative things. We called and the receptionist was able to fit us in within a few days of the diagnosis. Excellent directions were provided, and while it takes an hour and fifteen minutes to reach, you literally start on the road in front of our house, make two right turns, and you are at the oncology clinic.
Nancy and I both arranged to be available to take Clondike for the first appointment. I find it interesting how the experience affected Nancy and me differently. The clinic is in a new, bright, airy building, but it was a zoo that day. The overflow of dogs (and the occasional cat) were being treated in the lobby and a number of three-legged dogs hooked up to IVs were being walked in the front yard. Nancy was appalled that so many dogs have cancer, while I was inspired by the number of owners who are going to the trouble and expense to treat them.
The oncologist saw the book Janet had loaned me under my arm and said "I see you have been doing some reading. I have much better numbers than you will find in there." Once again, Nancy was somewhat put off by the statistical nature of oncology, while I figured someone who is proud of her "numbers" is going to go to great lengths to maintain her record.
The oncologist did a bone marrow test and determined that Clondike was at World Health Organization (WHO) stage IVa (with Vb being the worst stage). The "IV" was dictated by the fact that Clondike's spleen was enlarged but her bone marrow was clear. The "a" indicated that she was asymptomatic. The oncologist reassured us that the spleen functions as a sort of large lymph node and the fact that it was involved was not very significant. She said lymphoma is a very treatable cancer and gave us a brochure on a patented monoclonal antibody treatment. She asked if we wanted to start treatment that day, and since the nodes had grown alarmingly in the previous two weeks, we said "yes." The first treatment was a simple injection of L-Asparaginase which took seconds.
The basic protocol prescribed for Clondike (modified VCAA) called for two cycles of four chemotherapeutic agents (L-Asparaginase, Vincristine, Cytoxan, Adriamycin--generally one per week). If the patient was then able to hold a remission for three weeks, monoclonal antibody treatments would be given on five successive days. One frustrating aspect of lymphoma is that there is no lab test to determine the activity of the cancer. Remission is defined as the absence of swelling in the lymph nodes, and of our veterinary team, only the oncologist had the experience to make this determination with certainty.
The monoclonal treatments were not chemo in the traditional sense and most dogs tolerated them very well. The oncologist was getting an average six-month remission time measured from the end of monoclonal therapy and was able to re-induce remission in a higher percentage of patients than with more traditional protocols. Research with this protocol also indicated that successive remission times could be 75-80% of the duration of the previous remission, considerably better than the 50% usually quoted in literature on chemotherapy. (NOTE: This therapy became unavailable shortly after Clondike was treated with it due to legal complications with the lab licensed to produce it.)
We were being bombarded with information and it was a really scary time, but then the vet Nancy works for loaned her the January, 1996 issue of Veterinary Clinics of North America: Small Animal Practice which was entitled "Controversies in Clinical Oncology." It contains two excellent articles giving an overview of various chemotherapeutic protocols for canine lymphoma. It was the most valuable resource we found and made us feel we were on the right track.
Finding a Holistic Vet.
Clondike had the second treatment in the protocol without incident and then it was time to visit the holistic vet. Unfortunately this was not a good experience. After a drive of more than two hours, we got a two-hour lecture, with no time for our questions. We got a lot of valuable information, but also knew immediately that we needed to find another holistic vet.
After yet more research we located a holistic vet who has a clinic only 45 minutes from our house and specializes in adapting traditional Chinese medicine to veterinary patients. Both holistic vets agreed that acupuncture was more likely to excite the cancer cells than to suppress them. The second holistic vet gave us slightly different nutritional advice from the first one, but also suggested a Chinese herbal regimen. The Cancer Support Formula contains 14 herbs, only two of which are intended to fight the cancer directly. The rest support the body and help it deal with chemotherapy. The Chinese approach to cancer therapy is to seek a balance where the patient can live with the cancer, and this seems to be a good complement to chemotherapy.
We saw the holistic vet every three or four weeks, and he fine tuned Clondike's herbal mixture based upon his exam. While the effect of the herbs was too subtle to state with certainty that they helped with either the cancer or the chemo, they did noticeably reduce Clondike's episodes of night panting attacks. Our general practice vet was very supportive of our search for complementary medical advice and she frequently faxed lab results to the holistic vet to keep him up to date on Clondike's progress from a Western perspective.
Clondike the Weird.
The oncologist had told us the first day that dogs tolerate chemotherapy much better than humans, and that only about 10% of dogs experience serious reactions. Except for a few curly coated breeds, they also seldom experience hair loss.
Clondike tolerated the first two treatments well and was evaluated in full remission. Then things took a turn for the worse with the third chemo treatment. Cytoxan is administered in pill form over four days. We got through all four doses and were congratulating ourselves on Clondike's lack of a reaction when she started to throw up. This continued for three days and was accompanied by severe diarrhea. It required a trip to the vet for IV fluids and injectable anti-nausea drugs to bring the reaction under control.
We approached the fourth drug with great trepidation, but the oncologist reassured us that a reaction to one drug did not increase the chances of reactions to other drugs. Adriamycin, the "gold standard" for lymphoma treatment in both dogs and humans, is administered as an IV solution. Clondike seemed to be doing well and we confidently expected her to be able to attend the Penn-Dutch Pyrenean Fun Day at the end of July. We had houseguests who had come all the way from England to attend this event.
Well, the Brits had no sooner set foot in the house and been greeted by Clondike than she started to throw up. This was a much more violent nausea than with the Cytoxan and it was soon obvious that we needed help. So off we went the next morning to our local vet clinic where Clondike was admitted for the first time in her life. They were so full they had to put her in the cat wing the first night--ah, the stories she could tell. Her stay lasted eight days.
Barry and Pat Denyer from England had planned their vacation around our Fun Day and had hoped to meet some Pyr people and visit some Pyr kennels. We did all of that, but they also got a firsthand look at American veterinary medicine in all its forms. During their two week stay they visited Clondike in the hospital at all hours of the day and night. When she was released (after the Fun Day, unfortunately) they accompanied us to the oncologist's office. We even managed to get them over to meet the holistic vet and observe an acupuncture treatment for another Penn-Dutch Pyr.
While Clondike was hospitalized with the Adriamycin reaction we were introduced to a miracle drug called Neupogen, a product of genetic engineering. This expensive drug stimulates the bone marrow to produce more white blood cells and is very beneficial for patients, human or canine, undergoing chemotherapy. Clondike's total white count went down to 900 (6,000 is low normal) and the vets suspected she was getting pneumonia. We made a quick trip to the oncology clinic to pick up a dose of Neupogen and Clondike responded overnight. The vets at our local clinic were amazed at the speed with which this drug works.
In addition to the nausea and diarrhea, Adriamycin is known to damage the heart muscle in some patients. Clondike's cardiologist (that's another story) had done an ultrasound exam the day she received the Adriamycin and found no problems. As she recovered from the reaction, Clondike's lungs were still "noisy" and we dreaded what a repeat cardiac ultrasound might reveal. In this case we got a pleasant surprise, as the cardiologist gave Clondike a clean bill of health.
At our next visit to the oncologist, the staff conferred concerning how we might prevent or minimize reactions in the future and then the oncologist came back into the examining room and told us we had one "weird" dog. We said we preferred "eccentric." The oncologist explained that with large dogs the difference between a therapeutic dose and a toxic dose is much smaller than for a smaller dog. She also said that she hadn't treated many Pyrs, which is good for the breed, but meant that any chemo agent given to Clondike was essentially experimental.
During the second cycle Clondike sailed through the first two treatments again, but all of the oncologist's best efforts were not enough to prevent a reaction to Cytoxan. Clondike also developed a cardiac syncope (low heart rate) which led to seizure-like episodes when taking Zofran, the ultimate in nausea control medication. This led to further cardiology consults.
We did a lot of soul searching before deciding to at least listen to what the oncologist might propose for how to administer the next dose of Adriamycin safely. She surprised us by suggesting that we skip it and go right to the monoclonals. Clondike had no problem with these treatments and we hoped for a long remission.
The Hair Thing.
While Clondike began to feel better as soon as she was off chemo, she didn't look better. The various shaved places from the biopsy and chemo treatments were not growing back in and she was losing undercoat at a rapid rate. A thyroid test soon revealed the reason--a TT4 of zero! Clondike's regular vet feels that it was the reaction to the Adriamycin, rather than the chemo itself, that threw the thyroid out of kilter. With Soloxine Clondike soon began to grow hair and look her old self. She was able to attend the tailgate party following the Penn-Dutch fall Specialty in September and was courted by two of her most ardent admirers, neither of whom seemed to mind her "punk look."
Clondike had a great fall and we became complacent, sure that each bi-weekly visit with the oncologists would be routine. In early December, however, after 16 weeks of post-chemo remission, the lymph nodes came back up and the oncologist immediately treated Clondike with L-Asparaginase. Even though we knew the best chemotherapy has to offer is a long remission, we had dared to hope for a cure and were hit pretty hard by the return of the cancer. Clondike, however, was feeling fine, and had never really experienced any symptoms directly attributable to the cancer. This made the guilt over the Adriamycin reaction all the greater.
The first Vincristine treatment seemed to bring the nodes down somewhat, but we obviously were not getting the kind of response we had the first time around. A second treatment with Vincristine had little effect on the cancer and may have contributed to a neurological weakening of Clondike's hind end. It looked like we were not going to get a full remission without Adriamycin, and we weren't sure Clondike could tolerate another reaction.
Rather than proceed with Cytoxan, the oncologist recommended something brand new--a protocol called DMAC just developed at the Ohio State Vet School. She said it was basically a rescue protocol designed for patients who no longer respond to the first line drugs, but it is supposed to be easier on the digestive tract than most other protocols and it uses entirely different drugs which don't activate the multi-drug resistance (MDR) gene in the cancer cells. She still thought we might want to try Adriamycin at some point, but felt that this new protocol would not preclude that.
DMAC consists of two combinations of drugs administered one week apart. This cycle is then repeated, usually for a total of five to eight cycles (10-16 weeks). The first treatment is a four-hour IV drip which could not be administered until the next day. We decided to try it and I felt better when another owner I met while Clondike was "dripping" said her dog was on the second DMAC treatment and seemed to be responding with no side effects.
Clondike's response was almost unbelievable! Within 12 hours of the first treatment her nodes went down dramatically (the first line drugs had taken four days to show any effect)! By the next week the oncologist evaluated her in full remission and we advanced to the second treatment. Unfortunately, this caused a fairly severe reaction involving some 12 hours of vomiting followed by a few days of diarrhea. The nodes went down even farther, however, and a 24-hour hospitalization for fluids restored Clondike to fair condition.
We repeated the first DMAC treatment and experienced another drop in white count that necessitated a dose of Neupogen. Then the oncologist said "let's wait and see how she does." We waited and waited and managed to eke out a 12-week remission.
Third Remission and Another Reaction.
The nodes came back up in May and we began another course of DMAC. Clondike sailed through the first treatment, but had a lowered white count. Neupogen was administered and she experienced a reaction to it unprecedented in the annals of canine oncology as far as we can determine. About 24% of human patients experience a pain reaction as the drug kicks in. This is usually controllable with OTC pain relievers, but sometimes requires narcotics. Clondike experienced what we think was this pain response, although as far as we can determine from an Internet search, no veterinary oncologist has ever encountered it before in a dog. Clondike continued to surprise the vets!
We advanced to DMAC treatment two and even with injectable anti-nausea drugs administered every eight hours (I had gotten pretty good at giving subcutaneous injections--not particularly difficult with all that loose skin on a Pyr), Clondike managed to vomit several times an hour for 14 hours. The injectable Centrine did manage to control the diarrhea, and the nodes totally disappeared!
Unfortunately Clondike experienced yet another problem. Because her white count remained high following DMAC treatment #2 during the first series of treatments, we neglected to perform a CBC this time around. At noon on Saturday, eight days after the chemo treatment and minutes after the close of regular office hours at our local vet clinic, Clondike began to shiver. Her temperature was 106 degrees and when we called the clinic, the technician told us to put ice under her armpits and bring her right in.
Her temperature continued to rise to 107 degrees and her white count had fallen to 500! I had been keeping a dose of Neupogen in the refrigerator at home, but, of course, I hadn't thought to bring it to the clinic. So I made a quick trip home while Nancy and the vet got Clondike settled on ice packs out in the barn. By the time I got back to the clinic, the vet had given Clondike a painkiller called Banamine which had brought her temperature down to 103 degrees. The vet administered the Neupogen and we stayed at the clinic for several hours to monitor Clondike's temperature and watch for any reaction to the Neupogen.
When her temperature had stayed down below 102 for several hours we took Clondike home and monitored her temperature every two hours all night. She was NOT amused! She experienced what we think was a very mild pain reaction to the Neupogen at about eight hours after it was administered. She just went off by herself and was grumpy for about three hours. We felt the Banamine minimized the reaction and discussed with the oncologist using it or something similar if Neupogen were required again.
Clondike's temperature remained in the normal range overnight and Sunday began with a trip back to the clinic for another CBC (Our local clinic provides true 24-hour emergency service and is staffed by highly qualified technicians seven days a week). Clondike's white count had climbed to 3,200 and her regular vet felt she was on the mend. By Monday her white count reached 8,200. The vets believed the elevated temperature was a side effect of the low white count and not the result of an infection, although antibiotics were administered as a precaution.
When we returned to the oncologist on Friday, she decided that Clondike's nodes were so far down that we could discontinue chemo and monitor Clondike's progress. We were encouraged by the fact that Clondike responded almost as dramatically to the DMAC drugs this time as on first administration. We thought a nine-week remission (75% of 12 weeks) was not an unreasonable thing to hope for, and we hoped that Clondike might surprise us and do better than that.
Clondike did better than anyone had expected and remained in full remission for 20 MONTHS, which turned out to be the rest of her life. On our first visit to the oncologist she quoted an average life expectancy of 14 months and Clondike more than doubled that. DMAC was so new that there was little track record of what to expect, but in general it yields shorter remissions than the first line drugs and for many dogs it "doesn't do squat." So Clondike was out on the frontier of veterinary medicine, blazing new trails.
The Bottom Line.
New advances in veterinary cancer therapy are being made every day, but the process can be very time consuming and expensive, and it won't always be successful. Unfortunately some dogs with lymphoma are diagnosed too late for treatment to be effective. Clondike's case is right out of the textbooks--a client notices a lump while grooming or playing with the dog. With Pyrs the folds of the neck make it especially hard to notice swollen lymph nodes.
Then there is the cost. Our oncologist estimated $1,500 for the first remission and I believe that is realistic for a dog with no complications. Clondike's care for the first year cost over $13,000, much of that for supportive and complementary care. The costs break down as follows:
To put this in perspective, about half of Clondike's food requirements are included in the above expenses in the form of prescription diets and supplements, and she incurred almost $4,000 in vet bills in the year prior to diagnosis due to infections resulting from a compromised immune system. It is open to question whether the weakened immune system lead to the cancer, or was a symptom of a pre-cancerous condition. None of the vets has offered more than a guess on this issue.
If faced with a diagnosis of lymphoma and a limited budget, discuss options with your vet and/or oncologist. Most chemo agents used in the basic protocols are available as generics and some form of chemo should be within the realm of possibility for many owners. Keep in mind that the vast majority of dogs will sail through chemotherapy with few side effects, which will greatly reduce costs.
The commitment of time may be an even more pressing concern than money. Nancy and I work odd shifts that allow for a lot of flexibility in scheduling vet appointments. Also, being near the University of Pennsylvania allowed us to find qualified specialists within driving distance, which may not be possible in many areas. Even when Clondike was in remission, we tried to follow the oncologists' recommendation for bi-weekly checkups. These provided us with a lot of help in managing a geriatric cancer patient, but the 2 1/2 hour round trip every two weeks could be draining for us. Clondike, however, ran laps in glee at the mention of a "road trip" and thoroughly enjoyed the attention she received at her various veterinary appointments.
Finally there is the nursing care required. While in remission, Clondike took more than 30 pills and capsules twice a day. Some of these needed to be given on an empty stomach, some exactly one half hour before food, and some with food. When on chemo she took fewer pills (we were cautious of antioxidants' possible interference with chemo), but she received a subcutaneous injection of Centrine twice a day and sometimes took a drug called Carafate which is a coating agent sort of like a super Pepto Bismol. It is given twice a day and must be separated from food and medications by at least two hours--a very difficult feat to manage around a busy work schedule.
We were fortunate to have had the resources in time and money (well, credit anyway--my Master Card cracked from being run through so many vets' machines) to allow us to provide Clondike the best treatments available. Many owners will find ways to accomplish this, but it isn't easy. The good news is that cheaper, better tolerated protocols are being developed all the time.
The Complementary Approach.
We employed a number of "alternative" approaches to Clondike's care. We prefer to think of them as complementary and we made it clear to both holistic vets that we wanted to support chemotherapy rather than replace it. Our holistic vet has mentioned how nice it is to work with traditional Western practitioners, as many clients come to him as a substitute for traditional cancer therapy. With lymphoma, naturopathic therapies used alone seem to yield disappointingly short life expectancies, while they have been known to help achieve very long remissions when used with traditional chemotherapy.
I want to emphasize that every food, supplement, vitamin and drug which Clondike was given was either prescribed or approved by at least one of her medical team, all licensed veterinarians. There is so much bad information floating around that I can't emphasize enough the importance of finding vets that you trust and discussing all aspects of your pet's care with them.
People ask if it was worth the time and expense. For us the answer is an unqualified "yes!" Clondike was our surrogate child, and had an intense love of life that never dimmed, even when the chemo made her very sick. While it would have been nice if she had been one of the 90% of dogs who tolerate chemo with few side effects, she had 31 good months out of her last 32, and that is probably 30 more than she would have had without treatment.
She spent Christmas 1998 on her "country estate" in Virginia (click here for photos) and had the opportunity to visit Janet Ingram. She has traveled to Chicago and shown in Veterans class at a National Specialty (click here for photos), received two dozen roses and lots of goodies on Valentine's Day (click here for photos), sniffed innumerable sniffs, made dozens of therapy visits and been named "Dog Hero of the Year" by the Tails on Wheels pet therapy group in Texas, recognizing her therapy work and courage in facing cancer treatment.
Clondike lived life to the fullest, inspiring several other dog owners to try chemotherapy for lymphoma, and she provided her vets with clinical data on the DMAC protocol. On February 8, 2001 at age 13 1/4 (ancient for a Pyr) she had to be euthanized, basically for medical problems relating to old age. Upon announcing her passing on the Internet chat lists I received over 150 messages of condolence, a tribute to Clondike's strength of character and the power of the Web.
Today (in 2008) I still receive an average of 2 e-mails a week either asking for information, or just expressing appreciation for the message of hope which Clondike's story evokes.