"Rational treatment planning requires an accurate diagnosis, complete staging, and knowledge of expected tumor behavior with regard to local growth and propensity for developing regional and distant metastases. Many treatment options are available for the management of cancer, and each has its advantages and disadvantages. Clinicians must recognize the strengths and shortcomings of each treatment modality, and apply therapy toward efficacious treatment of each aspect of expected tumor behavior ( i.e. local, regional, and distant disease). Currently multdisciplinary treatment is employed most commonly to maximize treatment results while minimizing related toxicity. Combinations of surgery, chemotherapy, and radiation often can more effectively eradicate cancer, especially multifocal cancer, than any one modality alone. The goal of treatment is to maintain the highest quality of life for the longest period of time.

A Key Point is this: The probability of long-term tumor control is greatest when aggressive therapy is instituted early, before the tumor is disturbed by previous failed therapeutic attempts."

"Chemotherapy is most useful for regional and disseminated neoplasms. It is used primarily for palliation; few cures are achieved. Some cancer types are notably chemosensitive. Lymphoid neoplasia and transmissible venereal tumors often are treated effectively; most other non-lymphoid tumors are only moderately sensitive. Chemotherapy is useful, however, for treatment of many tumor types as adjunct therapy to other treatments or for palliation."

Principles of Chemotherapy

"Use only drugs with documented activity against the specific tumor type

Administer all drugs at maximum tolerated doses and intervals. (Dr. Johnson's comment: the definition of maximum tolerated dose may vary from individual to individual, and from one veterinarian to another.)

Some protocols are administered in two phases: an initial phase of intensive therapy (induction), followed by a period of less frequent drug administration (maintenance).

Combination chemotherapy using agents with different mechanism of action and no overlap in toxicity results in enhanced cancer cell destruction, reduced induction of drug resistance, and reduced toxicity.

Continue chemotherapy past the time of complete remission because microscopic tumor remains after clinically detectable tumor has resolved."

Common Chemotherapeutics Agents Used In Veterinary Medicine

"Alkylating Agents include: Cyclophosphaide (Cytoxan; Mead-Johnson), Chlorambucial (Leukeran: Burroughs-Wellcome:, Melphalan (Alkeran; Burroughs-Wellcome, Cisplatin (Platinol; Bristol:, Carboplatin (Paralatin: Bristol)

Antimetabolites include: Methotrexate (Lederle), 5-Florouracil (Roche), Cytosine Arabinoside (Cytosar-U; Upjohn).

Plant Alkaloids include: Vincristine (Oncovin; Eli Lilly)

Antibiotics include: Doxorubican (Adriamycin; Labs), Mitoxantrone (Novantrone; Lederle)

Hormones: Prednisone

Miscellaneous: L-Asparaginase (Elspar: Merck, Sharp & Dohme)"

"Radiotherapy is primarily useful for local and regional neoplasia. In selected cases, it is used for palliation of painful disseminated tumors.

Radiotherapy is administer as a single modality or is combined with surgery, chemotherapy, or hyperthermia. It can be administered:

As the initial form of therapy (neoadjuvant radiotherapy)

Concurrent with other therapies (intraoperative radiation, concurrent chemotherapy or hyperthermia)

As postoperative therapy (adjuvant radiotherapy)"

Tables of Relative Radiation Sensitivity for Selected Canine and Feline Tumors are available in surgery and oncology textbooks.

"Hyperthermia: Heat is an effective adjunct therapy because it enhances the cytotoxic effects of radiation and many chemotherpay agents. Hyperthermia is induced locally by ultrasound or radiowaves or implemented as whole body hyperthermia induced by a humidified chamber or radiant heat device.

Immunotherapy: Immunotherapy has emerged with renewed potential. Because neoplastic cells may be immunologically different from healthy cells, selective or nonselective induction of the host immune system by various biologic response modifiers (e.g., bacterial agents, interferons, monoclonal antibodies, lymphokines) may enhance elimination of tumor cells, Immunotherapy appears to have the greatest potential as an adjunct to other therapies to eliminate microscopic residual tumor.

Phytodynamic Therapy: Many tumor cells selectively accumulate certain systemically administered photoactive chemicals. Tumors then are exposed to light of selected wavelengths (laser light), and the photoactive substances become cytotoxic. Various photoactive drugs and light sources currently are being tested. Early results indicate that photodynamic therapy may be useful for treatment of localized solid tumors."

"Many animals with cancer have alterations of metabolism that result in malnutrition. When severe, these alterations result in the clinical syndrome of cancer cachexia. Malnutrition impairs the immune system, inhibits wound healing and normal cell repair, and increases treatment morbidity and mortality.

Factors contributing to malnutrition include:

Anorexia

Decreased nutrient intake

Metabolic or digestive abnormalities that cause inefficient or inappropriate use of nutrients

Treatment-related factors such as therapy-induced nausea and vomiting"

"Treatment is directed toward early elimination of cachexia syndrome (by elimination of neoplasia) and supportive care to minimize its effects during the interim. Nutritional support is provide by enteral or parenteral feeding and should be provided when patients do not eat for more than 5 days or have greater than 10% acute loss of body weight. Laboratory results indicative of malnutrition include hypoalbumnemia ( low serum albumin), lymphopenia (low number of lymphocytes in complete blood count), and anemia (low red blood count, packed cell volume, and hemoglobin)."

"Pain can contribute significantly to development of inappetence, weight loss, reduced mobility, depression, and poor interaction with the owner.

The severity is determined and a treatment protocol implemented to provide adequate analgesia with minimal sedation and other side effects. Therapy is by use of local or regional anesthesia, or with systemic treatment using transdermal delivery of narcotic-based pain medication, or orally administered nonsteroidal anti-inflammatory agents, and narcotics."

Euthanasia: "When treatment options fail, and an animal’s disease is progressing, consideration of euthanasia may be appropriate. Owners are encouraged in advance to establish limits for their pet’s level of deterioration." If it comes time for euthanasia, Dr. Johnson always sedates and anesthetizes the patient before giving the final injection. This way there is no pain or memory of the experience. Although these pre-euthanasia drugs add to the cost for the doctor, this is no time to cut corners. These situations are always tough for everyone: the family, relatives, friends, the veterinarian, and the veterinary technician.

The credit for many of the above excerpts goes to Saunders Manual of Small Animal Practice (Birchard, Sherding), Saunders.

The North American Veterinary Conference is the largest veterinary conference in the world. Dr. Johnson attends this conference every year.

What Is New In Canine and Feline Lymphoma: Dr. Argyle, BVMS, PhD, MRCVS, School of Veterinary Medicine, University of Wisconsin, Madison, WI.

"Lymphoma is one of commonest forms of malignancy encountered in small animal practice. It is characterized by the malignant proliferation of lymphoid cells which can arise in any organ containing lymphoid tissue. Lymphoma occurs most commonly in middle-aged animals (median age 6-9 years). Airedales, Basset hounds, Boxers, Bulldogs, St. Bernards, Bull Mastiffs, and Scottish terriers are at increased risk. In cats, FeLV remains the commonest cause of lymphoma."

Single Agent Therapy. "Dogs can be treated with prednisone alone, but this will provide only a short remission. Dogs pretreated with steroids are more difficult to drive into complete remission if the owner subsequently decides to opt for more aggressive chemotherapy. Doxorubicin is the best agent to use, if the client desires the simplicity and convenience of single agent use and is willing to accept a shorter predicted survival."

Combination Chemotherapy

"UW-Madison Protocol (19 week protocol for dogs). This protocol consists of L-asparaginase ( at the beginning), cyclophosphamide, hydroxydaunorugicin (doxorubicin), oncovin (vincristine), and prednisone. Cancer remission rate is 85-90% with median survival of 10 to 12 months. 25% of patients can be anticipated to survive longer than 2 years. Occasional patients are ‘cured’ (survival over 4-5 years)."

Feline Lymphoma

Alimentary – "characterized by gastric, intes5tinal, or mesenteric lymph node involvement. Most cats with alimentary lymphoma are FeLV Elisa negative. For those cats with solitary intestinal lesions surgery and chemotherapy is the treatment of choice. For cats with the diffuse form of small cell lymphoma than a protocol consisting of daily prednisolone and Chlorambucil (pulsed every weeks) offers a good treatment modality."

Renal – "enlarged kidneys, and renal failure are typical feature of feline renal lymphoma. Most affected cats are middle-aged and FeLV ELISA negative."

Mediastinal – "most cats with mediastinal lymphoma are relatively young and FeLV ELISA positive. Typical signs include difficulty breathing, exercise intolerance, coughing, and abnormal heart sounds."

Multicentric – "unlike the situation in dogs, this is a relatively uncommon form of feline lymphoma."

The Role Of Radiation In The Management Of Lymphoma In Dogs

"Lymphoma in dogs is very sensitive to the effects of radiation. The use of total body irradiation to treat multicentric disease has been limited by the lack of hematological support and autologous bone marrow transplantation that would be required to treat complications."

"Mast cell tumors (MCTs) are the most common canine skin neoplasms comprising 7-21% of all skin an subcutaneous tumors. A breed predilection is seen in Boxer dogs, but they also have increased numbers of the benign form. Dermal MCTs may metastasize to regional lymph nodes, liver, spleen and bone marrow but very rarely metastasize to the lungs.

The most important prognostic factors for canine MCTs are the histologic grade of the tumor and the completeness of excision."

Treatment:

"Surgery is the mainstay of therapy for Grade 1 and 2 tumors. Grade 2 tumors with lymph node involvement should have the affected lymph node excised and biopsied to confirm spread and are treated with chemotherapy as a follow up. Grade 3 tumors may be treated surgically if the owner is aware of the guarded prognosis and if no signs of gross systemic spread are found. Chemotherapy is recommended even if the margins are clean or if the tumor is nonresectable."

Radiation: "MCTs are very radiosensitive but radiation is best used as an adjunct therapy for incomplete margins after surgery."

Chemotherapy: "When localized therapies are appropriate only as palliation for discomfort or mechanical obstruction, the most frequently recommended drugs are corticosteroids."

"One protocol presently used at the University of Wisconsin Veterinary Teaching Hospital is vinblastine and prednisone. DCNU (Lomustine) is another drug which has shown promise.

Histamine blockers are used preoperatively with large masses or for life with no resectable masses or systemic disease. Cimetidine or famotidine reduces gastric acid production ."

Feline Mast Cell Tumors

"Splenic Mast Cell Tumors. MCT primary to the spleen in cats is most common in older non purebred cats. Staging includes a CBC, biochemical profile, urinalysis, FeLV, FIV, thoracic radiographs, abdominal ultrasonography, and bone marrow aspirate. Fine needle aspiration cytology or biopsy of spleen is indicated. The diagnosis is sometimes made form ascitis fluid or blood smear. Treatment may include splenectomy. The use of corticosteroids is controversial. Chemotherapy with CCNU or vinblastine has not been reported. Supportive therapy consists of antihistamines.

Intestinal Mast Cell Tumors. Consider surgery where indicated. Adjunctive therapy has not been described, but consider chemotherapy with prednisone or CCNU. Other drugs such as vincristine, L-asparaginase may have anecdotal success.

Cutaneous Mast Cell Tumors. Cutaneous MCTs are common in all age cats; and Siamese are predisposed. Surgical excision is usually curative but new lesions may arise. Corticosteroids are probably not effective. Adjunctive therapy for incompletely excised tumors consists of radiation therapy."

"Epidemiological studies in man have demonstrated a protective effect of chronic aspirin intake in the incidence of colorectal cancer. Further, the use of anti-inflammatory drugs to abrogate tumor growth has shown promise in several animal model systems and clinical cancer cases. Active research is underway in several laboratories to identify the cellular mechanisms mediating this effect. The majority of NSAIDSs (Non-steroidal antiinflammatory drugs) inhibit the isoforms of cyclosoxygenase (COX-1 and COX-2) to varying degrees or are selective for one isoform. The COX inhibition, antiinflammatory and antitumor effects in-vivo are exerted in a parallel dose-dependent manner. Nevertheless, the mechanaism by which NSAIDs cause protective and direct antitumor effects is still to be determined."

Dr. Johnson’s comment: In the February 23, 2004 edition of Time magazine, appeared an article entitled "The Fires Within", Inflammation is the body’s first defense against infection, but when it goes awry, it can lead to heart attacks, colon cancer, Alzheimer’s and a host of other diseases. In 2000 researchers concluded that patients who take Celebrex, a prescription drug from Pfizer that was orginally designed to treat inflammation in arthritis, are less likely to develop intestinal polyps. Now there are dozens of clinical trials of Celebrex, testing , among other things, whether the medication can also prevent breast cancer, delay memory loss, or slow the progression of the devastating neurodegenertive disorder known as Lou Gehrig’s disease.

Dr. Robert Tepper, president of research and development at Millennium Pharmaceuticals, in Cambridge, Mass. stated that "Virtually our entire R & D effort is now focused on inflammation and cancer!"

On February 27, 2004, Genentech received approval from the FDA on its colon-cancer drug, Avastin, which targets one of the growth factors released by the body as inflammation gives way to healing.

According to Dr. Argyle, "dogs with neoplastic disease treated with NSAIDs are usually selected on the basis that standard therapy has failed, is precluded on medical grounds, is declined by the owner, or does not exists. Owners commonly report that the patients receiving piroxicam, a NSAID appear to have an improved quality of life, manifested as increased activity and alertness. The increased COX-2 selectivity of meloxican or other selective COX-2 inhibitors makes for an attractive alternative to piroxicam in the treatment of cancer, since it may reduce possible gastrointestinal side effects." Dr. Johnson’s comment: Just recently, Zuprin (Tepoxalin) a new NSAID was passed for use in dogs. Zuprin is both a COX-1 and COX-2 inhibitor. This drug is already showing promise in Dr. Johnson’s referral practice.

"Biphophonates are analogues of pyrophosphate and are potent inhibitors of osteoclastic bone reabsorption. Their use in metastatic bone pain is becoming widely established in human oncology. In the dog, systemic pamidronate and zolidronate have been used anecdotally. In human oncology these agents have been shown to impact greatly on morbidity in patients with bone lesions from multiple myeloma or breast cancer."

"Soft tissue sarcomas (STS) are tumors of mesenchymnal origin that are grouped together under the name STS due to similar biologic behaviors. Also known as spindle cell tumors, STS include fibrosarcoma, hemangiopericytoma, neurofibrosarcoma, schwannoma, liposarcoma, and malignant fibrous histiocytoma. STS can arise both in the cutaneous/subcutaneous tissues and in internal organs, but as the internal organ tumors have a more aggressive biologic behavior, most discussions of STS refer only to cutaneous/subcutaneous locations. In general, STS are very locally invasive yet have a low metastatic rate."

"STS occur primarily in middle-aged to older dogs, and no breed or sex predilection has been identified. The masses are located in subcutaneous tissues and are often firm and adhered to deeper structures. They may be irregular and when very large may be ulcerated and secondarily infected. A biopsy is usually needed for a definitive diagnosis. Imaging modalities may be employed to evaluate the primary tumor and assess the potential for surgical cure, to further assess for metastatic disease, or to plan radiation therapy – radiographs, CT or MRI of the primary tumor, and abdominal ultrasound are additional diagnostic imagining techniques that may be indicated depending upon the location of the tumor."

"A key point to remember is that STS have a false appearance of encapsulation. In reality, this ‘capsule’ is made up of normal host and tumor cells that have been compressed together by rapid tumor growth. These tumors are locally invasive and wide margins are needed to surgically remove them completely. Surgery is the treatment of choice for most soft tissue sarcomas. Radiation therapy is an excellent adjuvant therapy for soft tissue sarcomas. Chemotherapy is not very effective against measurable disease."

It has often been suggested that acupuncture is contraindicated for animals with cancer. Some feel that the movement of Qi will cause cancer to metastasize more quickly. This can be true if needling is done close to, or surrounding tumors. The experiences of many practitioners show that acupuncture can be safely used with cancer patients and can have tremendous benefits. (This has been Dr. Johnson's experience)

Acupuncture is usually not a primary treatment for cancer. Typically, veterinary patients use surgery, radiation, herbs, chemotherapy, nutrition, and various forms of supplementation as the foundation for treatment of cancer. Acupuncture can enhance any of these modalities and one shouldn't fear causing harm. Any form of cancer therapy should be done, foremost, to enhance the well-being of the animal, and if the cancer should go in to remission as well, then the practitioner is doubly blessed.

Patients with osteosarcoma, hemangiosarcoma, and bladder cancer often present with excess heat and stagnation. Treatment would include points to drain damp, clear heat, and toxicity (List presented with comments).

Keep in mind with excess animals that cancer could not have taken hold unless there was some weakness, even if it was relative. The surgery, drugs, and stress these poor creatures undergo merit tonification of some kind, even if it's in the form of some strengthening foods )(vs. all draining/cold foods) or a helper herb. (Dr. Johnson's comment: in his practice this almost always includes acupuncture). 

Some animals have patterns that appear excess and deficient. (Dr Johnson sees many patients that have excess and deficient organ systems at the same time). They may pant a lot or be polyuric/polydypsic. There is usually a history of low-grade chronic disease. The focus is on moving and tonifying blood.

Remember that the Spleen can only produce blood when it is strong. Dr. DiNatale went over acupuncture points that are useful.

Animals on chemotherapy have very special needs. It's important to find out the protocol to be used, and use prophylactic needling around the time of treatment. Intestinal problems usually occur within 24 hours to one week post treatment. The drugs may cause stomach and intestinal disharmony, producing panting, straining, foul diarrhea, gurgling intestines, vomiting of bile or food, and anorexia. Dr. DiNatale described points that are helpful in harmonizing and dispersing.

Bone marrow suppression usually occurs towards the middle to the end of the week following chemo. Patterns are Liver Yin deficiency and Liver Blood deficiency. Dr. DiNatale describes points which are helpful.

Herbal formulas high in polysaccharides, such as those that contain high concentrations of mushrooms and Astragalus, have bone marrow protective effects. Herbal treatment once bone marrow suppression is evident should be based on tounge and pulse to avoid overheating, overdrying, or creating dampness. (Dr. Johnson's comment: TCM evaluation should be backed up with routine chemistry, complete blood count, and a platelet count)

In 1997, Dr. R.M. Clemmons published an article on the "Integrative Treatment of Cancer in Dogs" It is available on the University of Florida Veterinary Teaching Hospital website. Although published 8 years ago, most of his comments are still relevant. For those interested in this presentation, click on Dr. Clemmons/Integrative Treatment of Cancer in Dogs

RECENT ALTERNATIVE & COMPLEMENTARY ANTI-CANCER THERAPIES

Indole –3- Carbinol (I3C)

Many of our clients are familiar with tamoxifen’s mode of action against breast cancer in that it blocks estrogen. What’s not usually appreciated is that tamoxifen has other modes of action. The other actions are just as important, or in some cases more important, than the estrogen-blocking effect. And they are not unique to tamoxifen. Indole-3-Carbinol has been shown to have a similar action.

Tamaxifen also works in estrogen receptor-negative breast cancers and progesterone receptor-positive breast cancers. This is because tamoxifen not only blocks the estrogen "grow"signal, it blocks another type of "grow" signal known as protein kinase C (PKC). PKC is another one of those contact points inside the door jamb, and blocking this signal stops cancer genes from activating. PKC also controls cell growth and transformation signals.

Indole 3 Carbinol works by this same mechanism, and is one of the major anticancer substances found in cruciferous (cabbage family) vegetables. It is a member of the class of sulfur-containing chemicals called glucosinolates. It is formed from parent compounds whenever cruciferous vegetables are crushed or cooked. Indole-3-carbinol and other glucosinolates (i.e.sulforaphate) are antioxidants and potent stimulators of natural detoxifying enzymes in the body. Indole-3-carbinol and other glucosinolates are believed to be responsible for the lower risk of cancer in humans that is associated with the consumption of broccoli and other cruciferous vegetables like cauliflower,cabbage, and kale.

Indole-3-carbinol has shown promise in laboratory animals, pet animals and humans, and has not been shown to have harmful side effects or drug interactions.

Indole-3-carbinol is available for oral administration in capsule form. This form has not been shown to have any negative side effects.

Further information on Indole-3-Carbinol can be found on following website. Click www.iherb.com  for access, then click indole-3-carbinol. The article is well referenced.