CONVENTIONAL MEDS USED IN LOW DOSE ALTERNATIVE WAYS:
Piroxicam
Pubmed Cit:
Palliation with chemotherapy: The addition of chemotherapy
to radiation therapy has not resulted in significantly improved survival
times. It is, however, often effective
in relieving clinical signs. Median
survivals of 5 months are reported for patients with nasal adenocarcinoma
treated with cisplatin chemotherapy (J Am Vet Med Assoc 200[3]:355-357 Feb
1’92). A more recent study presented at the
Veterinary Cancer Society meeting in 2003 showed survival ranges of 5-32 months
when doxorubicin, carboplatin and piroxicam
were used in combination.
Piroxicam -COX generic anti-inflammitory with
antiangiogenesis properties. Most COX do not do antiangio well.
Piroxicam Links:
A new treatment for canine malignancies is
available. Piroxicam, a non-steroidal, anti-inflammatory drug, is now in
the treatment arsenal of veterinarians. Sold under the trade name
Feldene, piroxicam is a popular prescription familiar to many as a human
arthritis medication.
The interesting point for STCA members is that prioxicam is
showing an effectiveness in treating maliganancies to which Scotties seem to
have a greater risk than some other breeds. Quoting the 1986 Scottish
Terrier Club of America Handbook article Diagnosis and Treatment of Some Common
Malignancies in the Scottish Terrier, "it would appear that genetics plays
a significant role in the development of cancer. Epidemiologic studies
have shown that the Scottish Terrier has a higher than expected incidence of
lymphosarcoma, bladder carcinoma, oral melanoma, cancer of the skin (squamous
cell carcinoma and mast cell sarcoma), and to a lesser extent, nasal carcinoma
and gastric carcinoma." (1)
These are the same malignancies which recently have been
treated with good results in piroxicam studies at Purdue University School of
Veterinary Medicine. This new therapy has meant a much improved quality
of life in a 10-year-old female Scottie of mine. She was diagnosed with
transitional cell carcinoma of the bladder in September 1992. Surgery,
radiation and chemotherapy all give quite disappointing results with this type
of bladder cancer, indicates the above 1986 STCA cancer review. We are
pleased with the results of piroxicam therapy.
THE HISTORY:
Lucky, our old C.D. obedience dog, started having
accidents in winter, 1991, at 9 years old. Urinalyses on several
occasions revealed no infection, though there were microscopic traces of
blood. Our local veterinarian, Dr. Scott Burt, Big Spring, TX, suggested
diethylstilbesterol (DES), an estrogen therapy that can help female incontinence
caused by weakening of the muscles that control bladder action. But he
cautioned that the accidents and straining to urinate might be evidence of
early bladder malignancy. Routine blood work not long after had shown
elevation of the serum alkaline phosphatase enzyme which sometimes indicates
presence of malignancy. Cancer ws a distinct possibility. And,
affirmed the 1986 STCa cancer article, "It can be extremely difficult to
differentiate clinically between chronic bladder infection, stones and
cancer."
DES seemed to improve the situation temporarily.
Lucky headed for college as a bed-dog for our son Scott. Later, off at
school, there were more accidents. This time blood was in the urine,
obvious to the eye. Home Lucky came in June, 1992, for a recheck.
Dr. Burt x-rayed for possible bladder stones or a malignant growth. There
was no evidence of either.
By September, 1992, Lucky's puddles were centered with
large spots of blood. Dr. Burt ran positive and negative cystograms,
radiologic dye studies of the bladder. This time the news was defenite,
and bad. There was a growth at the neck of the bladder. It was so
obstructive to the pathway into the bladder that Dr. Burt could not use the
usual French 8 catheter to insert dye into the bladder. He had to resort
to the smallest French 3«. Cell studies at Texas Veterinary Medical
Diagnostic Laboratory confirmed Dr. Burt's tentative diagnosis of transitional
cell carcinoma of the bladder.
The options? Surgery, radiation, chemotherapy, or nothing.
The nearest surgical specialist was 300 miles away. Even for a specalist,
the tumor would be hard to reach and tricky to excise completely. Dr.
Burt predicted that the tumor's location probably would require breaking
Lucky's pelvis, and that the delicacy of operating at the narrow neck of the
bladder would make it nearly impossible to remove all the malignancy.
Prognosis, even with surgery, would not be good. There isn't much hope
for transitional cell carcinomas.
Breaking her pelvis would guarantee Lucky would complete
her life as a cripple, and the surgery also might leave her totally
incontinent, instead of only partially. Our family decided we couldn't
put a 10-year-old dog through such trauma. We opted to let our dog live
out whatever time might be left as normally as possible at home.
The first two weeks after the cystogram were not
good. There were more accidents than ever, with large quantities of
blood. Lucky was listless. She lost a pound, a noticeable loss for
a 15-pound Scottie that never misses a meal.
Sadly, we figured Lucky had only a very few weeks left and
took her back down for a college weekend and a final farewell to Scott.
That weekend was full of last photos. I investigated cremation. We
expected the end soon.
Back in Big Spring, the nice surprise was that there was
still something we could try. Dr. Burt had checked with oncologist at
Texas A & M University College of Veterinary Medicine. Clinicians
there were having some success with piroxicam cancer therapy pioneered by
Purdue's vet school. Oncologist Dr. Claudia Barton suggested we use
piroxicam with Lucky.
Dosage prescribed for a dog the size of a Scottie required
me to reformulate the drug. I became something of a pharmacist. The
10 mg capsules are too strong for a Scottie. Recommended dosage is 0.3
mg/kg every 48 hours. For Lucky's 15 pounds, that means three doses per
capsule. One capsule lasts six days. To prevent breakdown of the
drug because of its possible instability in liquid, I mix one capsule at a time
with pharmaceutical syrup. The mixture is split between three syringes
(to be given orally) and refrigerated until used.
In the Purdue clinical trial reported in a 1992 issue of
Cancer Chemotherapy and Pharmacology, piroxicam was given to 62 dogs. A
fairly complete range of cancers was studied. Tumor types were 10
transitional cell carcinomas, 10 melanomas, 9 osteosarcomas, and smaller
numbers of fibrosarcomas, hemangiopericytomas, squamous cell carcinomas,
mammary adenocarcinomas, perianal gland adenocarcinomas, anal sac
adenocarcinomas, lymphomas, mast-cell tumors, nasal carcinoma, mammary adenoma,
transmissible veneral tumor, synovial cell sarcoma and lipoma. Though no
complete remissions occurred, eight partial remissions were documented in 3 of
the 10 dogs with transitional cell carcinoma of the bladder, in 3 of the 5
animals with squamous cell carcinoma, in 1 of 3 dogs with mammary
adenocarcinoma, and in the one dog with transmissible veneral tumor.
Complete tumor remission in two dogs bearing malignant
hemangiopericytoma and metastatic carcinoma was observed in an earlier Purdue
study using piroxicam. A previous human clinical trial of piroxicam with
31 cancer patients having pulmonary metastasis also had shown one complete
response and give "minor regressions" of malignancy.
Additionally, Purdue later reported use of piroxicam in 24
dogs, all with transitional cell carcinoma of the bladder. These tumor
responses at 60 days were 0 complete remissions, 4 partial remissions, 11
stable diseases, and 8 progressive diseases. Preliminary analysis showed
a median survival of 150 days (range 30 to 510 days) with 8 dogs alive at the
time that the report was written.
Veterinarians at Texas A & M have used piroxicam
therapy for about a year and have been pleased with the results.
"the good thing about piroxicam therapy is that the dogs feel pretty
good," said oncologist Dr. Barton. She notes, "We still
recommend radiation followed by surgery, if the tumor is in a site where it can
be reached."
Dr. Barton does not claim that piroxicam is a miracle
drug. She describes results at Texas A & M which are similar to those
at Purdue: about dogs responding with decreased tumor
size, with stable disease, and with progressive
disease. "But," she emphasizes, "that's better than other
results we've had."
The results at Texas A & M have been obtained with
half the dose originally used in the 1992 Purdue research, and patients have
exhibited fewer gastrointestinal problems.
Piroxicam can cause serious GI bleeding like any NSAID taken continually,
according to Dr. Barton. (JUST GIVE PEPCID PLUS USE METRONOMIC ALTERNATING
PROTOCOLS)
"We have tested the tumor size with sonography.
It does appear tumors get a little smaller with piroxicam," indicates Dr.
Barton. "There may be some chemotherapeutic benefit, but we're not
particularly impressed with tumor shrinkage." She explains that
improvement may be due to reduced edema and reduced inflammation rather that
true tumor reduction.
"We feel like piroxicam
gives comparable results to those we get with cisplatin chemotherapy or
radiation," say Barton. The advantage, Dr. Barton repeats,
is: "the dogs feel good, and they get to stay at home. "
Disadvantages Barton ascribes to the common cisplatin chemotherapy include
severe nausea, vomiting and kidney toxicity. And with radiation treatment, dogs must be hospitalized four to five
weeks for the 12 to 15 treatments, according to Barton.
Purdue also compared its piroxicam results to similar
cases treated with cisplatin, the currently used chemotherapy in canine
transitional cell carcinoma. The tumor
response and survival date of the two drugs were similar, but the toxicity of
piroxicam treatment was much less that that of cisplatin treatment, according
to Purdue.
From my own experience with a Scottie, piroxicam has been
a bit of a miracle. We expected a steady deterioration and speedy demise
of our pet. Instead, five months after beginning piroxicam therapy our
dog acts like a 10-year-old puppy. Next month she will be 11. The
first three months of treatment Lucky almost stopped having accidents, and the
ones she had weren't bloody. The fourth month of treatment she did start
having frequent accidents again, and they remain bloody. (2) However,
Lucky feels good!
The only side effect of piroxicam therapy has been an
occasional day with minor nausea and spitting up. There's an occasional
time like the morning she tipped over her bowl of kibble and tried to bury the
food disgustedly under her kennel rug. Two hours later her belly must
have been back to normal. She knocked the same bowl off a crate top to
get at every crunchy bite and then scavenged a jar of throw-away bacon grease
from the trash.
Lucky retains her great interest in food. She is
active, can still work up a game of soccer. She delights in life and
appears in no pain. What more could we wish for a cancer patient?
Without treatment of any kind, transitional cell carcinoma
of the bladder can claim a dog's life in a very short time, as little as one to
three months or less, according to Dr. Barton. With piroxicam therapy,
Dr. Barton projects a more usual survival time of 9 months.
At this point, it's been about a year from what must have
been Lucky's first signs of bladder cancer, and five months since diagnosis of
cancer and beginning treatment with piroxicam. We still have milestones
ahead with Lucky. We had our one more Christmas, now maybe one more
birthday next month, perhaps even one more walk in the neighborhood 4th of July
parade. The end has not changed, but piroxicam has been a gift of time,
more importantly, a gift of quality time.
For future reference, please write the following addendum
in your 1986 STCA Handbook following the article, "Diagnosis and Treatment
of Some Common Malignancies in the Scottish Terrier".
CANCER UPDATE, 1993--
Piroxicam (Feldene)
therapy is being used with good results in treatment of some canine
malignancies. Recent suggested regimen: 0.3 mg/kg piroxicam every
48 hours.
Reference: Dr. Claudia Barton, Professor of Oncology,
Texas A & M University College of Veterinary Medicine, College Station, TX.
Bibliography:
"Piroxicam Therapy in 24 Dogs with Transitional Cell
Carcinoma of the Bladder." D. W. Knapp, R. C. Richardson, et
al. Proceedings of the 9th Annual ACVIM Forum, New Orleans, LA, May,
1991. p. 896.
"Phase I Trial of Piroxicam in 62 Dogs Bearing
Naturally Occurring Tumors." D. W. Knapp, R. C. Richardson, et
al. Cancer Chemotheraphy and Pharmacology. 29: 214-218, 1992.
Footnotes:
(1) Of genetic interest is that one litter mate of
our Lucky is known to have died with transitional cell carcinoma at about 9
years old. Lucky's breeder is deceased, so we do not know if these are
the only two closely related dogs in that line to have had transitional cell carcinoma.
Lucky is a spayed female, and was never bred, so implications in her own
offspring are impossible to determine.
(2) During the first several months of her piroxicam
therapy, Lucky received Vitamin C supplementation daily, unrelated to her
cancer treatment and unprescribed by a veterinarian. About 1,000 mg
ascorbic acid crystals were added to her evening meal. For no special
reason, I stopped Vitamin C supplementation, then about two months later added
it to Lucky's diet again. I noticed that, upon receiving Vitamin C again,
Lucky almost immediately had fewer accidents and that there was much less blood
in them. Thinking back, the time when Lucky stopped receiving Vitamin C
was about the time she started having bloody and frequent accidents. I
have no scientific evidence that Vitamin C is a hepful adjunct of piroxicam
therapy, but I can't help but wonder. I have sent this information to Dr.
Barton for her comment.
Carprofen as Alternative?
Meloxicam / Metacam also. I read that Metacam is easier on the stomach.
Recently,
subtotal prostatectomy with a neodymium: yttrium-aluminum-garnet laser has been
suggested as palliative treatment for prostatic neoplasia with and without
metastasis.44 Subtotal prostatectomy was followed by a
one-time injection of interleukin-2 (4.5 million IU in 1 ml normal saline) into
the remaining prostate and ongoing once-daily administration of 0.1 mg/kg
meloxicam (an NSAID that primarily inhibits cyclooxygenase [COX]-2).44 The survival time of eight dogs that underwent
this treatment protocol ranged from 5 to 239 days (median: 103 days), and
postoperative urinary incontinence did not develop in any dog. Medical
treatment with COX inhibitors alone has also been advocated in dogs with
prostatic carcinoma.53 Inhibition of COX-2,
which is expressed by 88% of prostatic carcinomas,53 is thought to result in a decrease in tumor
cell proliferation, an increase in apoptosis of tumor cells,
and inhibition of tumor angiogenesis. Dogs
treated with COX inhibitors (e.g., piroxicam, carprofen)
survived significantly longer than dogs that did not receive NSAIDs, with a
median survival time of 6.9 months and 0.7 month, respectively.53
Can't Live with out it (piroxicam)
“My dog byron who is 6 years old has nasal cancer. Our vet
gave him a 3 month life expectancy. They put him on this medication and ever
since then he has been doing great. He is now on month 5 and is larger then
life, he hasn't changed a bit. He is just as happy as he was if he was still a
puppy. “
Treatment.
Dogs were given piroxicam (Pfizer,
New York, NY) at a dosage of 0.3 mg/kg every
24 h p.o., alone for 4 weeks, followed by piroxicam combined with
cisplatin (60 mg/m2 i.v. every 21 days). Cisplatin was provided by
Bristol Laboratories, Bristol-Myers Squibb Co., Princeton, N.Y. Diuresis was
induced by administering 0.9% saline i.v. at a rate of 18 ml/kg/h for 4 h
before and 2 h after cisplatin administration. Then, saline was given at a rate
of 5 ml/kg/h for 15 h. Cisplatin was administered i.v. over a 20-min period.
Butorphanol (Torbugestic; 0.4 mg/kg i.v.; Fort Dodge Laboratories, Fort Dodge,
IA) was given 30 min before cisplatin to decrease vomiting.
Results
Antitumor Activity and Toxicity of
Piroxicam/Cisplatin.
Subject characteristics are summarized in
Table 1.
Fourteen privately owned pet dogs were enrolled in this study. Dogs had no
other major co-morbid diseases. Two dogs received three doses of cisplatin,
five dogs received two doses of cisplatin, and seven dogs received one dose of
cisplatin. Two dogs were not evaluated for piroxicam/cisplatin response because
of early withdrawal from the protocol caused by toxicity. The toxicity
associated with piroxicam/cisplatin is summarized in Table 2. Tumor
response, apoptotic index, proliferative index, and bFGF and VEGF
concentrations are summarized in Table 3.
Survival.
The median survival for 14 dogs was 329
days (range, 97–1000 days), with one dog still alive at 973 days. Seven dogs
survived more than 1 year. (CHEMO ALONE
DOES NOT EXTEND LIFE USUALLY, MORE PALLIATIVE. THE COMBO DID EXTEND, SO
PEROXICAM MUST BE THE DEAL WITH INF AND ANTIANGIO)
Induction of Apoptosis.
THIS SAME RESULT occurred
WITH NASAL ADENOCARCINOMA IN A FEW STUDIES.
What about ALTERNATING Doxycycline usage with Peroxicam?
The metronomic protocols are always using a Peroxicam
with either low dosage Chemo and or the old antibiotic Doxycycline.
One of the cheapest, safest, and most easily obtained
through a vet? Doxycycline. Now, doxycycline is not a dream antibiotic.
It actually has fairly limited use as an antibiotic. Some use it
for dental infections, but it is most commonly used to treat certain blood
parasites.
Some exciting news about doxy? It has anticancer
effects!
Doxycyline helps suppress angiogenesis (new blood vessel
formation that feeds tumors and robs the body). In this way it slows tumor
growth. It blocks enzymes called matrix metalloproteinases (MMP’s) that digest
the tissue around tumors, allowing new blood vessels to be formed. Check it out
here.
Not having access to as much blood supply, the cancer
cells are less able to metastasize through the circulation. This lessens
the spread of some cancers. http://www.ncbi.nlm.nih.gov/pubmed/12486404
In the lab, this drug can induce apoptosis (normal,
healthy, programmed death) of cancer cells. This is a direct action on
the cancer cells, and may have some usefulness in cancers like lymphosarcoma.
My opinion and usage of above research in Lucy's Cancer:
I simply opted to use what the above meds were doing and replace with naturally occurring substances in their whole form. Anti-inflammatory COX-2 , Apoptosis (normal programmed cell death), and Anti-Angiogenic (slowing down of blood vessel formation to tumor) herbs and supplements used.
View the list of stuff I use for Lucy and why.
