Dog Nasal Cancer Symptoms and Treatments

Dog Nasal Cancers Rare but Deadly

This article appeared in a Vet Magazine I found.

*things in parenthesis are my input

"Nasal passage cancer generally develops very insidiously in older pets. (my dog is only 7 though...)

It is rare in cats and not common in dogs. (not common? then why do I find when I talk to people in general in my town, someone more often than not says 'oh, I know so and so whose dog had it!) It composes about 1 percent of feline tumors and up to 2.5 percent of canine tumors. Long-nosed breeds (dolichocephalic) and senior dogs are at higher risk.

Clinical Signs
The early signs of nasal cancer in dogs or cats are unilateral nasal and/or ocular discharge, epistaxis, stridor, loss of smell, loose teeth and sometimes pawing at the face. (don't forget sneezing and that weird hard reverse sneezing)

Late-stage signs may include a facial deformity along the dorsal aspect of the maxillary bones or over the paranasal and frontal sinuses. Some cases develop a raised or pitting facial bone deformity.

Some cases may exhibit a firm or soft focal, raised mass protruding around or between the eyes. Some cases may have a palatine deformity from the softening and bowing out of the hard palate due to demineralization of the palatine bone and growth of the mass.

In every case of facial deformity, there is bone lysis and tumor invasion at that site. If the lesions extend into the brain, seizures and behavior changes are often exhibited. (there are meds that help this)

A complication of nasal cancer is the over production of mucus. It collects and clogs the nasal passages and sinuses.

Prepare the Owner
The stridor and mess from sneezing out phlegm along with the vivid color of blood during episodes of epistaxis cause great distress for pet owners. (IT SURE DOES! I stopped the bleeding using the chinese herb Yunnan Bai Yao. Here is a link to info)

Most animals with nasal cancer exhibit sporadic signs in the early stages, then show progression over a period of about three months before diagnosis.

Initially, the clinical signs fit the assumption that the pet has one of a variety of nasal conditions. Most clinicians would suspect or that a foreign body is lodged in the nasal passages.

A search for the offending material finds nothing. If the nasal passages are cultured, pathogens are often found and identified on culture and sensitivity reports.

So, the diagnosis of rhinitis may suffice for a time. Some elder pets have oronasal fistulas from infected or extracted teeth to complicate matters.

If the symptoms persist, the working diagnosis is often presumed to be either a foreign body that remains wedged in the upper turbinates or chronic rhinitis.

In some case histories, the nasal passages were explored several times without locating a foreign body yet no biopsy or culture was taken. (GEEZ JUST GET A BIOPSY)

Since the problem is presumed to be either infectious or allergic, the patient is placed on symptomatic treatment with antibiotics, steroids and antihistamines or nose drops for topical therapy. (good luck with the nose drops...)

The patient often gets relief from symptoms. This is why most nasal cancers go undetected for three months and why some cases may go undetected as long as six months in dogs and up to two years in cats.

Diagnosis
The best radiographs for visualizing the nasal cavity are taken under general anesthesia with the X-ray film placed into the open mouth for an intranasal view. $300

Teach your X-ray technicians to use the positions from a good radiology text for open-mouth studies of the nasal cavity.

Place the X-ray film inside the mouth. Place one corner extending as far back toward the tonsils as possible and take a DV image. This provides the best exposure of the nasal passages.

Intra-oral radiography is best accomplished with high quality non-screen film; we use mammography film.

The A-P skyline position for the best view of the frontal sinuses of the skull is also very important to complete a full skull series. Look for space occupying or lytic disease in the nasal passages or sinuses. Look for an asymmetrical density or lysis or interruption of the fine scroll pattern of the nasal turbinates, a break in the fine lines of the nasal septum or a density in one of the frontal sinuses.

Too many cases of nasal cancer are initially missed on the first X-ray series because of poor visualization.

Magnetic resonance imaging or computerized tomography scans of the nasal passages and paranasal sinuses have become the gold standard for imaging nasal tumors. Localization of the lesion is necessary for treatment planning.

A small number of patients may have lymphadenopathy. It is important to discuss the usefulness of MRI or CT scan in this setting with the pet owner. ($1000)

CT technology is used for computerized treatment planning for radiation therapy patients. So, if the patient will be receiving radiation therapy, it may save time and money to order a CT scan from the start.

Since general anesthesia is needed for these studies, it may be the best opportunity to also request tissue samples for definitive diagnosis. Some imaging services are set up to accommodate biopsy procedures and some are not. I prefer to refer cases to facilities that will do a biopsy.

Something New Mr. Shelton, an engineer, with a 10-year-old black Labrador retriever named B.J., taught me a new way to deal with night stridor for affected dogs.  I tell clients that their pet can breathe through the mouth despite occlusion of the nasal passages. When dogs are having difficulty with sleep, we try to have clients devise ways that their dogs can breathe through the mouth while sleeping.  Mr Shelton used a Milk Bone and a rawhide bone wedged between B.J.’s front teeth. At first. I suggested using a toy waffle ball for B.J. Mr. Shelton devised the perfect solution for his playful dog. He cut holes in a tennis ball because B.J. loved to hold her tennis balls for hours. This was a natural extension for her. She slept with the ball in her mouth in comfort without stridor. — A.V (hey not a bad idea!)

Biopsy
If a geriatric patient is going to be anesthetized for X-rays, a biopsy should be done at the same time. The radiographs will suggest the best area to sample.

Various instruments can be used but all require precautions to avoid penetrating the ethmoid plate. Rhinoscopy with direct biopsy of the abnormal tissues is most direct.

A long true-cut biopsy needle, a plastic cannula or biopsy forceps is passed through the nostril into the nasal cavity and thrust into the suspected lesion to harvest a sample for histopathology.

For safety, always measure the distance between the tip of the nose to the area just in front of the ethmoid (cribriform) plate. This should be just in front of the medial canthus. Mark the biopsy instrument with tape or ink.

In cases with nasal bone deformity or a bulge over a sinus, one can generally pass an FNA needle directly through the skin and softened bone into the lesion and aspirate a sample for cytology.

One can also insert a true cut instrument through the bulging defect and into the sinus to get a sample for histopathology.

In most cases, the harvested material is gelatinous and difficult to distinguish from phlegm. Expect bleeding and if necessary, use cotton soaked in epinephrine to pack the nostrils.

It may be necessary to keep the patient under anesthesia or quiet with sedation until bleeding is controlled.

Pathology
Pathology reports identify most canine nasal tumors as carcinomas. Most of them are respiratory adenocarcinoma followed by squamous cell carcinoma and a few miscellaneous or undifferentiated carcinomas.

About one third of nasal cavity neoplasia in dogs are sarcomas, with fibrosarcoma being most common followed by chondrosarcoma, osteosarcoma, lymphoma, and then other miscellaneous and undifferentiated sarcomas.

North Carolina State University summarized 320 cases of nasal tumors in cats, finding that 60 percent were carcinomas, 18 percent sarcomas and 12 percent lymphoma.

There is no correlation with grade and survival. However, some tumors may have a low mitotic rate or a slower rate of growth or a less aggressive biological behavior than others, such as low-grade chondrosarcoma.

Treatment
Surgery for dogs with nasal cancer was routinely performed until data showed that rhinotomy (opening the nasal passages and scooping tumor out) was a negative factor for survival time.

However, rhinotomy followed by orthovoltage radiation therapy yielded the longest survival times but rhinotomy was not necessary if the pet was to receive cobalt radiation therapy.

This information and the poor survival data made treating nasal tumors confusing and frustrating.

Today the norm is to avoid surgical rhinotomy. However, if pet owners are interested in radiation therapy, they should be referred for imaging studies to locate the extent of disease.

Then refer them to a radiation oncologist for consultation regarding the risk-benefit ratio and an honest survival time discussion based on the tumor type and the individual pet’s stage of disease.

The owner needs to reconcile his psychological, emotional, financial and ethical considerations regarding treatment for the pet. (up to $10,000 in total..... that is why I went the natural and holistic route and Lucy is past the average survival time of 4 months past diagnosis, she is at 7 months past diagnosis and she is in total remission)

Most facilities use cobalt radiation therapy and CT scan technology for treatment planning. Some facilities treat pets with linear accelerators. There may be no difference in the survival times with either machine, but side effects may be less severe in animals treated with the higher energy linear accelerators.

Of all nasal passage tumors, nasal lymphomas respond the best to radiation therapy as well as to chemotherapy.

Most oncologists recommend systemic chemotherapy in addition to radiation therapy for nasal lymphoma because lymphoma is considered a systemic disease rather than a focal disease. This is especially true in cats.

Drugs that enhance the effect of radiation (radiation sensitizers) such as mitoxantrone or carboplatin (some use low dose cisplatin) have been used. However, the advantage for survival is not yet firmly established.

I think it makes sense to use systemic chemotherapy because it may enhance the radiation’s effects and also addresses the metastatic potential.

This is important because 10 percent of patients present with lymph node metastases and 40 percent will go on to metastasize. Local recurrence and metastases are the main reasons for death of pets treated for nasal cavity cancer.

So, there is a need to keep searching for better ways to enhance local control and control of metastatic disease.

The side effects of radiation therapy for nasal cancer are quiet severe, especially if the tumor approaches the ethmoid plate or invades the orbit.

Patients experience radiation-induced oral mucositis, chealitis and conjunctivitis.

The client must be informed and prepared for the responsibilities of home care during and following treatments. Pet owners must also be told to expect chronic nasal discharge following treatment.

The normal delicate tissue of the nasal turbinates will never again function properly due to permanent injury from the radiation therapy. Cataracts and blindness following radiation therapy will occur if the orbit is invaded by the cancer and if the eyes are included in the treatment field.

Chemotherapy is often elected as a palliative and less aggressive therapy, especially in advanced cases that have poor prognoses. Many oncologists offer medical management for clients who decline conventional radiation therapy for their pets.

I like to use carboplatin rotating with mitoxantrone every 21 to 30 days for most adenocarcinomas and carboplatin rotating with adriamycin for sarcomas.

Case Report: Rufus Gleason Rufus, a 10-year-old male, black Labrador retriever, was referred with a history of epistaxis and stridor due to nasal passage chondrosarcoma. Rufus, a 10-year-old male, black Labrador retriever, was diagnosed with nasal passage chrondrosarcoma. After chemotherapy, he went into a 146-week remission, during which Rufus walked in many 10-K events and traveled across the country with his family. Courtesy of Trudy Gleason His owner declined radiation therapy for Rufus and requested a less demanding path of treatment. We recommended palliative chemotherapy and chemoprevention for Rufus. Six cycles of carboplatin chemotherapy at 300mg/M2 IV every 21 days were administered. These were followed by treatments every six weeks for six months, then every eight weeks for the following two years. We also kept Rufus on piroxicam at 10 mg once daily and IP-6 and beta glucan. During his prolonged 146-week remission and maintenance, Rufus walked in numerous 10K events and traveled across the country with his family. Facial deformity finally appeared and caused discomfort. Rufus was entered into our end-of-life pawspice care program with special attention to analgesia, and he lived two more precious months before euthanasia.  — A.V. http://www.veterinarypracticenews.com/vet-practice-news-columns/oncology-outlook/nasal-cancers-in-pets.aspx

I also use long-term doxycylcine as my antibiotic of choice and an NSAID such as piroxicam, deracoxib or meloxicam for pain control and their anti-angiogenesis action. (this can be a good idea, I have not needed it yet this is a basic metronomic protocol like Navy protocol)

Clinical improvement is often reported for pets on chemotherapy with reduction of epistaxis, sneezing, snorting, stridor, nasal discharge and pain relief. Patients do not seem to have extended life spans with chemotherapy but many seem clinically improved for a variable amount of time.

Prognosis
The prognosis is generally grave to very poor. Untreated dogs and cats usually die within two to seven months of diagnosis. If rhinotomy is the only treatment, survival is actually shorter.

In selected cases that receive radiation therapy (plus or minus adjuvant therapy), survival can be raised to a range of eight to 25 months.

The one-year treatment survival may be 40 percent and can go up to 80 percent in select cases. Half of the one-year survivors die in the second year. (remember burning your dogs face with radiation is not fun and takes quality time away and costs upwards of $6000-$10000 plus 3 weeks of almost daily radiation) Palliative chemotherapy may improve clinical signs for a time but does not seem to extend survival.

If you are trying to select a good case for radiation therapy, sarcomas do better than carcinomas and respiratory adenocarcinomas do better than other carcinomas.

Tumor size and location are also factors. Localized lesions in the rostral to middle part of the nasal passage do better; most are in the caudal two-thirds of the nasal passage.

Lymphomas respond the best and low-grade chondrosarcomas have the potential to survive the longest.

Radiation therapy for nasal passage cancer is a difficult process for the patient and caregivers. The risk-benefit ratio must be weighed carefully in each case.

Therefore, during consultation with the pet owner, it may be difficult to recommend conventional therapy over palliative therapy, especially for advanced cases due to the overall poor prognosis." end of article

(The stuff I researched DEEPLY and am posting on this blog put Lucy into full remission in 4 months) Please read all these posts about using alternatives. I am not broke and my dog is fine. Please spread this information. Your vet just is not going to be that much help. You need to use them as a tool to get any meds you might need like Prednisone (use only when bad and in the beginning) , antibiotics when needed, Low Dose Naltrexone (which you will have to talk them into) and pain meds. Use my information for everything else needed.

CONVENTIONAL MEDS USED IN LOW DOSE ALTERNATIVE WAYS

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.

Other studies also found that just using Piroxicam or P with doxo alternated worked almost as well!
 http://www.ncbi.nlm.nih.gov/pubmed/11809678

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671873/

Piroxicam -COX generic anti-inflammitory with antiangiogenesis properties. Most COX do not do antiangio well.

Piroxicam Links:

http://www.stca.biz/index.php?option=com_content&view=article&id=587:promising-new-treatment-for-malignancies&catid=320:cancer&Itemid=100 

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?

http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2002&PID=12984&Print=1&O=Generic

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 

http://mct.aacrjournals.org/content/2/2/183.full more on this

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.

http://growwings.blogspot.com/2006/09/canine-nasal-tumors.html piroxicam doxycycline testimonials

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.

http://www.dogcancerblog.com/an-antibiotic-for-dog-cancer/    DOXICYCLENE

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.

Anti-angiogenic Drugs in the Treatment of Canine Cancer

Anti-angiogenic Drugs
    For cancer cells to divide and become solid tumors they are dependent upon the formation of blood vessels, a process known as angiogenesis, that will provide blood flow with oxygen and nutrients to the developing tumor. Many cancer cells excrete molecules into the surrounding tissues that stimulate the formation of new blood vessels. Based on these observations, the novel idea of inhibiting tumor growth by cutting off blood supply to the tumor was developed. Natural and synthetic inhibitors of vascular formation, known as anti-angiogenic drugs, have been purified, formulated and assessed for their abilities as anti-tumor agents. Such drugs include angiostatin, thrombospondin, and endostatin. In preclinical animal studies, anti-angiogenic drugs have been found to significantly inhibit tumor growth and in some instances produce tumor regression.

Anti-angiogenic Drugs in the Treatment of Canine Cancer
Many of these anti-angiogenic drugs are in the early stages of clinical development for treatment of human cancers.     Dog-related News Article:  "Anti-angiogenesis: Perhaps a new way to address cancer"

Applications of Anti-angiogenic Drugs in the Treatment of Cancer

Antiangiogenic strategies and agents in clinical trials.
Rosen L.

Angiogenesis: new targets for the development of anticancer chemotherapies.
Gourley M, Williamson JS.

Angiogenesis and Cancer Control: From Concept to Therapeutic Trial.
Brem S.

Novel cancer therapies: more efficacy, less toxicity and improved organ preservation.
Joensuu H. ***For a more complete listing, enter the following format of search terms in the PubMed search window:  antiangiogenic-therapy AND cancer

Many health food store supplements have Anti-angiogenic properties. Take a look at Lucys pill list I give her.
Plus a few antibiotics like Doxycycline and NSAIDS like Metacam/Meloxicam/Peroxicam show these properties. This is called the NAVY protocol. Or Metronomic Protocol when each given on alternating days.

AntiAngiogenesis Meloxicam Peroxicam Navy Protocol

All cancerous tumors, for example, release angiogenic growth factor proteins that stimulate blood vessels to grow into the tumor, providing it with oxygen and nutrients. Antiangiogenic therapies literally starve the tumor of its blood supply by interfering with this process. A new class of cancer treatments that block angiogenesis are now approved and available to treat cancers of the colon, kidney, lung, breast, liver, brain, and thyroid, as well as multiple myeloma, bone gastrointestinal stromal tumors, and SEGA tumors. Some older drugs have been rediscovered to block angiogenesis, as well. These are being used to treatment angiogenesis-dependent conditions, such as hemangiomas, colon polyps, and precancerous skin lesions.

“This is a major leap forward for veterinary medicine,” said Dr. William Li, President and Medical Director of the Angiogenesis Foundation. “Eighty percent of dog cancers are identical to their human counterparts, so it makes complete sense that the antiangiogenic treatment approach that works in human cancers would also help dogs.” 

The Angiogenesis Foundation pioneered the first use of antiangiogenic therapies in canine cancers in 2000. Foundation researchers, working with veterinarians, developed a cocktail of human drugs suitable for dogs. Named the ‘Navy Protocol’ after a Golden Retriever that first received the treatment, the cocktail has been used to treat more than 600 dogs representing 32 breeds with 26 advanced tumor types.  Since 1995, the Foundation has been educating veterinarians and pet owners about the principles of angiogenesis and its promise for conquering cancer in dogs and other animals.

"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.

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.  And give with Pepcid keep GI problems down *according to some vet texts.  Talk to your vet about this. Meloxicam is newer and has less GI problems. These are human drugs too, so have your vet write the script for you to take to your pharmacy. It will be much cheaper. Vets make a HUGE markup on Rx.

NSAIDS for Cancer Therapy

Piroxicam, an NSAID, is a non-selective Cox-1 and Cox-2 inhibitor and has anti-cancer effects in dogs, which is well supported by the veterinary literature. Since those papers, veterinarians have prescribed other NSAIDS such as Deramaxx or Meloxicam, in lieu of Piroxicam, because these newer selective Cox-2 inhibitors are associated with lower rates of side-effects, such as GI ulceration and upset. It is assumed (but not known) that the anti-tumor effects are due to the Cox-2 inhibition, so it is also assumed that cox-2 selective NSAIDs should work as well as piroxicam.

However, this remains to be supported in the veterinary literature. (Not enough studies), but Piroxicam (and possibly other NSAIDS) remains a reasonable palliative option with careful monitoring.

Famotidine (Pepcid AC)

Available in 10 and 20 mg tablets OTC

Background

Stomach ulceration in humans is a prominent medical condition and there has long been pressure to develop effective and convenient ways to control it. Until relatively recently, we relied on simply neutralizing stomach acid by pouring alkaline solutions (i.e., Alka Seltzer, Tums, Rolaids, etc.) into the stomach. In fact, ulceration is a complicated process and there are many ways to address it.

Control of stomach acidity is an important factor in the treatment of stomach ulcers. Acid secretion is controlled by a hormone called gastrin (secreted in the presence of food and leading to secretion of stomach acid), acetylcholine (a neurotransmitter), and histamine (that same substance responsible for the unpleasant allergic effects of hay fever).

Famotidine is a special antihistamine, as are its cousins cimetidine (Tagamet HB) and ranitidine (Zantac). This class of antihistamine is not useful in combating familiar allergic symptoms (itching, sneezing, stuffy nose etc.) In allergy, histamine causes unpleasant effects by binding so-called H1 receptors. Famotidine, ranitidine, and cimetidine instead bind to histamine receptors in the stomach called H2 receptors.

Cimetidine was the first such H2 blocker available and each generation has brought about improvements in terms of fewer drug interactions and stronger effect. Famotidine is the longest lasting of the H2 blockers (usually one dose lasts 24 hours). Famotidine is 32 times stronger in its ability to inhibit stomach acid than is cimetidine and is 9 times stronger than ranitidine. A newer H2 blocker called nizatidine is now available that offers the additional advantages of especially rapid onset of action and some effect on normalizing stomach contractions as well.

Famotidine is currently available in an over-the-counter formulation making it highly convenient for pet owners to obtain (though obviously one should not consider using medications licensed for human consumption without specific instructions from one's veterinarian). Famotidine is especially useful for pets with chronic vomiting.

How This Medication Is Used

Famotidine is useful in any situation where stomach irritation is an issue and ulceration is a concern. It is often used in the treatment of Helicobacter infection, inflammatory bowel disease, canine parvovirus, ingestion of a toxin or medication that could be ulcerating (NSAIDs, like Metacam Meloxicam Peroxicam Duramaxx aspirin and others, for example), any disease involving protracted vomiting, or chronically in combination with medications which may have stomach irritating properties.

In diseases involving frequent vomiting or regurgitation, the esophagus (tube connecting the mouth and stomach) can be ulcerated by continuing exposure to vomit/stomach acid. Antacids are also helpful in this type of situation to reduce damage to the esophagus. Megaesophagus would be a condition where a long-acting antacid such as famotidine could be helpful in mitigating injury to the esophagus.

Side Effects

The H2 blockers as a group have a limited potential for side effects, hence their recent release to over-the-counter status.

There have been some reports of exacerbating heart rhythm problems in patients who already have heart rhythm problems, so it may be prudent to choose another means of stomach acid control in heart patients.

Interactions With Other Drugs

There are some drugs that are absorbed better in the presence of stomach acid (example: itraconazole). The dose of such drugs may require adjustment in the presence of famotidine.

Concerns and Cautions

The dose of famotidine may require reduction in patients with liver or kidney disease as these diseases tend to prolong drug activities.

It appears that famotidine is safe for use in pregnancy but should probably be avoided during lactation.