Lymphoma and beyond: Treating specific tumors (Proceedings)

Treating specific types of cancer can be very rewarding. The goals of this session are to muster your enthusiasm, increase your knowledge and hone your skills for treating cancer in your patients. It takes a positive attitude and clinical courage to treat cancer aggressively for any pet. More skill and thoughtfulness are required to successfully treat and care for fragile and geriatric cancer patients. As importantly, it often takes just as much courage to realize that a certain patient has passed the window of benefit from known conventional therapies at hand. Cancer is both insidious and resilient. Cancer often wins the battle despite the best effort of veterinarians and pet owners. However, the journey and rewards of treating and caring for veterinary cancer patients are well worth the effort. When pets are past the window of therapeutic benefit, palliative and Pawspice care comes to the forefront. We can develop this aspect of practice into an expected and respected care program for patients with advanced cancer. We will discuss the treatment of general types of cancer; lymphomas, adenocarcinomas and sarcomas.

Overview

We will look at the most common treatment protocols for the most common types of cancer. As new information evolves, we must expect to change and improve our protocols constantly. We must be aware of and be willing to incorporate innovative drugs, biotechnology and supportive supplements into our existing protocols.

Furthermore, we must be willing to adapt "mainstream" therapies to individual client and patient needs, even if that means we enter some "uncharted territory" with some innovative yet logical adaptations of known therapies. The most important objective must always be to provide the greatest benefit for the patient while respecting the emotional, financial, and physical capabilities of the patient's caregivers. This ultimate consideration will provide the best quality of medicine for the individual patient and client situation.

It should be no surprise that no two oncologists treat their cancer patients the very same way or with the same bedside manner. This explains why your clients will get different opinions and impressions from different consultants. Therefore, this paper will share the author's personal perspectives and approaches. Following a protocol assists you in "how to" treat a specific cancer. Rather than giving protocols, this author would like show "a way to" approach cancer in veterinary patients. Be advised that when you practice oncology, it is to prolong the human-animal bond with quality of life. Hopefully, these pages will help you minister a greater number of your cancer patients into a longer and higher of quality life.

Furthermore, we must be willing to adapt "mainstream" therapies to individual client and patient needs, even if that means we enter some "uncharted territory" with some innovative yet logical adaptations of known therapies. The most important objective must always be to provide the greatest benefit for the patient while respecting the emotional, financial, and physical capabilities of the patient's caregivers. This ultimate consideration will provide the best quality of medicine for the individual patient and client situation.

In addition, there are no two oncologists who treat their geriatric cancer patients the very same way or with the same bedside manner. This explains why your clients will get different opinions and impressions from different consultants. The editors asked me to share my personal perspectives and approach with you and tell you the way I treat my patients. This is not a "how to" but rather "a way to" approach to cancer in geriatric patients. There is really no secret or mystery about what I have been doing for the past 35 years. Thousands of clients and my editors felt that it was my duty to share my decades of experience admixing oncology and the human-animal bond. Hopefully, these pages will help you minister a greater number of geriatric cancer patients into a longer and higher of quality life. I hope to make a positive impact and encourage you to develop and practice the art of geriatric veterinary oncology.

Individualize Each Cancer Patient

Each cancer patient is unique, especially when you look at the bond shared with the family. Each patient is further individualized by the stage of disease, concurrent illnesses, the pet owner's economic situation, personal philosophy, time commitment and logistics regarding treatment choices. The protocols are often modified and adjustments in drug sequence and doses must be made to accommodate organ function and body score. If the patient is geriatric and afflicted with concurrent conditions, the recommended treatments must be adapted to that pet's individualized needs. It is not always easy to do this and stay within boundaries of the pet owner's wishes and finances. People will appreciate the integration of these principles into your approach for treating their pet's cancer. Such flexibility shows pet caregivers that you are considerate of the well being of their pet and that you respect their personal issues.

It is best to consult with an oncologist for the latest options to assist your client in decision making. The best local source to check would be your state's veterinary college, especially if they have an oncology service. Information on how to treat cancer abounds on the Internet. Check the class notes provided online by Dr. Neal Maudlin at www.vetmed.lsu.edu/oncology. Drs. Tony Moore and Angela Frimberger have an on line private oncology consultation service for veterinarians at www.vetoncologyconsults.com. Free medical information is available at www.MedScape.com. The National Library of Medicine hosts pubmed.gov with access to MEDLINE, its flagship database.

Veterinary Information Network offers "Vinners" interactive consultation and information at your fingertips to verify the latest treatment protocols with specialists in chat rooms at www.VIN.com. You and your clients can also download client-friendly free information from VeterinaryPartner.com. Members of Vetstream receive updated CD Roms on a quarterly basis containing the BSAVA Manual of Canine and Feline Oncology text by Dobson and Lascelles at www.vetstream.com. Online information will help you be aware of the most up-to-date cancer treatments for your patients.

The Three Musketeers of Cancer Therapy

Conventional cancer treatment utilizes three basic approaches: surgery, chemotherapy and radiation therapy. The coarse terms used for the three musketeer techniques are cut, poison and burn. It is beyond the scope of this one hour presentation to adequately review this extensive topic. Please see Table 6.3 (end) which has been adapted from Chapter 6 of the author's book, Canine and Feline Geriatric Oncology: Honoring the Human-Animal Bond, Blackwell Publishing, 2007.

Most clinicians make the decision to perform surgery upon a cancer patient with the blessings of their clients. However, it is often in the pet's best interest to consult a medical oncologist at the initial stages of treatment even before engaging a surgeon. Oncologists think differently about cancer patients, especially if the pet is geriatric. Oncologists think differently than surgeons, internists or radiation therapists do. They will generally try to get the diagnosis in an efficient, patient-sparing way. This is especially beneficial for the geriatric cancer patient that may be compromised with the effects of aging and other concurrent illnesses. Oncologists understand the growth rate of the various cancers and they will generally move more quickly toward definitive therapy following diagnostic procedures and interventions such as surgery.

Rather than postpone chemotherapy for the sacred two-week healing period following surgery, an oncologist may use neoadjuvant chemotherapy, radiation therapy or a combination of treatments before, during or shortly after surgery. This may prevent the patient's cancer from robustly skipping to a higher stage. Sometimes, waiting for the post operative healing period gives enough time for the malignant cells to recruit and recur. If the pet is scheduled for chemotherapy two weeks after surgery, the residual tumor gets the opportunity to undergo further cell divisions.

This author has witnessed the rapid recurrence of excised abdominal lymphoma in cats. Some tumors are back to presurgical dimensions within 10-20 days post op. One case comes to mind. A 17 year-old cat underwent a nephrectomy. The histology report diagnosed renal lymphoma. This old cat was presented to our service for management two weeks post nephrectomy. His remaining kidney was huge and the BUN and creatinine were elevated. A situation like this is very disappointing for pet owners. Clients readily consent to the recommendation for surgery, followed by a 2-3 week rest and recovery time, all in good faith. But the cancer, as in this case of lymphoma, may robustly move onward with its fatal agenda during this "waiting" period.

Feline Lymphoma

At the time of this writing, the only way to assess the prognosis for a cat with lymphoma is based upon the patient's response to chemotherapy.

Weezie, A 12 year-old M/S DSH started to decline and was taken to his local veterinarian for an exam. The doctor palpated an abdominal mass. Despite the fact that Weezie was eating and passing stool, the doctor recommended immediate exploratory surgery. The family requested more diagnostics. They were referred to a surgical specialist who performed an abdominal ultrasound to visualize the mass. The surgeon strongly recommended an exploratory surgery to remove the mass and biopsy even though Weezie was eating and passing stool. The owners felt that they were given no other choice. Therefore, surgery seemed like the best thing to do at the time. At surgery, a 6x8 cm mass was removed from the mesenteric nodes and intestine. The diagnosis was lymphoma and it was present in the kidneys, intestines and mesenteric nodes. The recommendation was to start chemotherapy after recovery. Recovery was uneventful and sutures were removed two weeks post op.

One week later, Weezie started to decline again. That is when I got that desperate night call. We fit Weezie in our schedule on the following day. A large abdominal mass was palpated along with an enlarged kidney with elevations of the BUN and creatinine. An oncologist would have approached this case much differently. A palpable mass in the abdomen of a FeLV negative geriatric cat is most likely lymphoma until proven otherwise. The cells can be characterized with persistent, diligent, percutaneous fine needle aspiration (FNA) cytology. Non-surgical evaluation techniques can diagnose lymphoma and avoid unhelpful surgery in cases like Weezie's. Surgery is valued and needed to harvest full thickness samples of intestine to definitively diagnose low volume intestinal lymphoma and to relieve obstructions.

In Weezie's case, the surgery and subsequent postponement of chemotherapy was not helpful. Chemotherapy for high-grade abdominal lymphoma in cats and dogs is very helpful if administered perioperatively within hours of the first few days following surgery. In the perioperative setting, it is best to omit prednisone for the first 7-10 days. We adjust the protocol to sequence the induction drugs over several days rather than administering them simultaneously. We must use the best window of therapeutic opportunity for the patient's sake. The clinician often feels caught in a medical dilemma; to wait until after healing of the surgical wounds vs. administering perioperative chemotherapy in time to halt the relentless growth of the lymphoma.

Lymphoma and Beyond

New technology now enables veterinarians to confirm the T vs. B-cell phenotype of canine lymphoma patients on cytology slides. Dogs with T-cell lymphoma have shorter remissions and survival times. Now we can identify which of our patients is afflicted with the more resistant T-cell form of lymphoma. With this help to guide us we can make adjustments for the patient's chemotherapy to use a more aggressive protocol. Immunotherapy has regained more respect in treating cancer. A monoclonal antibody MoAb231 was available in the past and there is interest in returning it to the market.(Jeglum 2008) (Crow 2008) We can also harvest cells from enlarged lymph nodes for the production of autologous DNA vaccines (the patient's lymphoblasts are transfected with a gene that encodes a serotyping antigen ) which might extend patient survival times. (Lawman 2008)

Combination chemotherapy is currently the most effective way to treat lymphoma. However, we have hit the survival wall at 10-14 months using conventional adriamycin based chemotherapy. Below you will find protocols for common tumor types used by the oncology service at The OSU. The first protocols listed are for canine and feline lymphoma. We will discuss various adjustments of the most commonly used protocols to accommodate patient needs based upon conditions such as obesity, osteoarthritis, heart disease, renal failure and diabetes. Attendees are encouraged to ask questions.

Table 6A.5 Protocols Used At The Ohio State University Veterinary Oncology Service

I. Lymphoma

A. Induction of remission

1. COAP protocol

Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, every other day for 8 weeks in dogs; (200-300 mg/m2 , PO, every 3 weeks in cats),

Vincristine (Oncovin® ): 0.5 mg/m2 BSA, IV, once a week, for 8 weeks,

Cytosine arabinoside (Cytosar-U® ): 100 mg/m2 BSA, IV or SQ, divided BID, for 4 days,

Prednisone: 40-50 mg/m2 BSA, PO, SID for a week; then 20-25 mg/m2 BSA, PO, every other day for 7 weeks.

In cats, cytosine arabinoside is used for only 2 days, and the remaining 3 drugs (cyclophosphamide, vincristine, prednisone) for 6 weeks rather than 8 weeks.

2. COP protocol

Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, every other day dogs; or 300 mg/m2 BSA, PO, every 3 weeks (dogs or cats)* ,

Vincristine (Oncovin® ): 0.5 mg/m2 BSA, IV, once a week,

Prednisone: 40-50 mg/m2 BSA, PO, SID for a week; then 20-25 mg/m2 BSA, PO, every other day.

* The duration of chemotherapy using this protocol is variable.

3. CLOP protocol

As in COP, but with the addition of L-asparaginase (Elspar® ), at a dose of 10,000-20,000 IU/m2 BSA, SQ, once every 4 to 6 weeks.

4. CHOP protocol (21 day cycle)

Cyclophosphamide (Cytoxan® ): 200-300 mg/m2 BSA, IV, day 10,

Doxorubicin (Adriamycin® ): 30 mg/m2 BSA, IV, day 1,

Vincristine (Oncovin® ): 0.75 mg/m2 BSA, IV, days 8, 15,

Prednisone: 40-50 mg/m2 BSA, PO, SID days 1-7; then 20-25 mg/m2 BSA, PO, QOD, days 8-21.

Sulfa-trimethoprim: 15 mg/kg, PO, BID

B. Maintenance

1. Chlorambucil (Leukeran® ): 20 mg/m2 BSA, PO, every other week;

Prednisone: 20-25 mg/m2 BSA, PO, every other day.

2. LMP protocol

Chlorambucil (Leukeran® ) and prednisone as above, plus methotrexate 2.5-5 mg/m2 BSA, PO, twice or 3 times a week.

3. LAP protocol

Chlorambucil (Leukeran® ): 20 mg/m2 BSA, PO, every other week;

Prednisone: 20-25 mg/m2 BSA, PO, every other day.

Cytosine arabinoside (Cytosar®) 200-400 mg/m2 , SQ, every 2 weeks, alternating with Leukeran.

4. COP protocol used every other week for 6 cycles; then every 3rd week for 6 cycles; and once a month thereafter.

C. "Rescue"

DOGS

1. D-MAC protocol: (repeat continuously for 10-16 weeks)

Dexamethasone 0.5 mg/lb, PO or SQ on days 1 and 8

Actinomycin D (Cosmegen®) 0.75 mg/m2, IV push on day 1

Cytosine arabinoside (Cytosar®) 200 -300mg/m2, IV drip over 4 hours, on day 1

Melphalan (Alkeran®) 20 mg/m2, PO, on day 8 (AFTER 2-3 DOSES OF MELPHALAN, SUBSTITUTE IN LEUKERAN AT THE SAME DOSE)

2. ADIC protocol

Doxorubicin (Adriamycin® ) 30 mg/m2 BSA IV, Q/3 weeks.

DTIC (Dacarbazine® ) 1,000 mg/m2 BSA, IV drip for 6-8 hours, once every 3 weeks.

3. L-asparaginase (Elspar® ) 10,000-30,000 IU/m2 BSA, IM, Q/2 or 3 weeks.

4. CHOP protocol if 2nd relapse on COAP or if good response to Adriamycin was previously observed in the patient.

CATS

1. Cytosine arabinoside (Cytosar-U® ): 100-200 mg/m2 BSA/day, IV drip for 6-24 hs.

Mitoxantrone (Novantrone®) 4 mg/m2, IV drip, mixed in the bag with the Cytosar.

Dexamethasone 0.5-1 mg/lb, PO, once a week.

Repeat ever 3 weeks.

II. Acute lymphoid leukemia (ALL)

COAP, CLOP, or COP.

III. Chronic lymphocytic leukemia (CLL)

1. Chlorambucil (Leukeran® ): 20 mg/m2 BSA, PO, every other week (with or without prednisone 20 mg/m2 BSA, PO, every other day).

2. Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, 4 days a week

Prednisone 20 mg/m2 BSA, PO, every other day.

IV. Acute myelogenous leukemia (AML)

1. Cytosine arabinoside (Cytosar-U® ): 100 mg/m2 BSA/day, IV drip or SQ (divided BID) for 4 days.

6 - Thioguanine (6 - TG® ) 40-50 mg/m2 BSA, PO, SID, or QOD.

2. Cytosar® and 6 - TG® plus Adriamycin® (10 mg/m2 BSA, IV, on days 2 and 4 of the cycle).

3. Cytosine arabinoside (Cytosar-U® ): 100-200 mg/m2 BSA/day, IV drip for 1-2 days.

Mitoxantrone (Novantrone®) 4 mg/m2, IV drip, mixed in the bag with the Cytosar.

Repeat ever 3 weeks.

V. Chronic myelogenous leukemia (CML)

1. Hydroxurea (Hydrea® ): 50 mg/kg, PO, divided BID, daily or QOD until normal white blood count.

VI. Multiple myeloma

1. Melphalan (Alkeran® ): 2 mg/m2 BSA, PO, SID x 1 week; then QOD.

Prednisone: 40-50 mg/m2 BSA, PO, SID x 1 week; then 20 mg/m2 BSA, PO, QOD. Can also be used at 6-8 mg/m2 , PO, for 5 days, repeating every 21 days.

2. CHOP protocol

VII. Mast cell tumors (systemic)

1. Prednisone: 40-50 mg/m2 BSA, PO, SID for a week; then 20-25 mg/m2 BSA, PO, QOD.

2. Prednisone: 40-50 mg/m2 BSA, PO, SID for a week; then 20-25 mg/m2 BSA, PO, QOD.

Cimetidine (Tagamet® ): 10 mg/kg, PO, QID (optional)

3. Prednisone: 40-50 mg/m2 BSA, PO, SID for a week; then 20-25 mg/m2 BSA, PO, QOD.

CCNU (Lomustine) 60-100 mg/m2, PO, q/3-4 weeks

4. CVP protocol

Vinblastine (Velban® ): 2 mg/m2 BSA, IV, once a week;

Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, QOD or 4 days a week.

Prednisone: 20-25 mg/m2 BSA, PO, QOD.

VIII. Soft Tissue Sarcomas - Dog

1. ADIC protocol (for spindle cell sarcomas)

Doxorubicin (Adriamycin® ): 30 mg/m2 BSA, IV, Q/3 weeks

DTIC (Dacarbazine® ): 1,000 mg/m2 BSA, IV drip for 6-8 hours; repeat Q/3 weeks.

Sulfa-trimethoprim: 15 mg/kg, PO, BID

2. VAC protocol (21 day cycle)[for other sarcomas]

Vincristine (Oncovin® ): 0.75 mg/m2 BSA, IV, days 8, 15.

Doxorubicin (Adriamycin® ): 30 mg/m2 BSA, IV, day 1.

Cyclophosphamide (Cytoxan® ): 200-300 mg/m2 BSA, PO, day 10.

Sulfa-trimethoprim: 15 mg/kg, PO, BID

IX. Soft Tissue sarcomas - Cat

1. Carboplatin (Paraplatin®) 200-280 mg/m2, IV, every 3-4 weeks.

2. AC protocol (21 day cycle)

Doxorubicin (Adriamycin® ): 1 mg/kg, IV day 1.

Cyclophosphamide (Cytoxan® ): 100-150 mg/m2 BSA on days 10 and 11.

3. VAC protocol (28 day cycle)

Vincristine (Oncovin® ): 0.5-0.75 mg/m2 BSA, IV, days 8, 15, 22.

Doxorubicin (Adriamycin® ): 1 mg/kg, IV day 1.

Cyclophosphamide (Cytoxan® ): 100-150 mg/m2 BSA on days 10 and 11.

2. MiC protocol (21 day cycle):

Mitoxantrone (Novantrone®): 4-6 mg/m2 , IV drip over 4 hours, on day 1

Cyclophosphamide (Cytoxan®): 200-300 mg/m2 , PO, on day 10

3. MiCO protocol(21 day cycle):

Mitoxantrone (Novantrone®): 4-6 mg/m2 , IV drip over 4 hours, on day 1

Cyclophosphamide (Cytoxan®): 200-300 mg/m2 , PO, on day 10

Vincristine (Oncovin®): 0.5 to 0.6 mg/m2 , IV, on days 8 and 15

X. Osteosarcoma - Dog

1. Cisplatin (Platinol®): 50-70 mg/m2 BSA, IV drip, Q/3weeks. Prior intensive diuresis is required.

2. Carboplatin (Paraplatin®): 300 mg/m2 , IV, Q/3-4 weeks

3. Doxorubicin (Adriamycin®): 30 mg/m2 , IV, every 2 weeks, for 6 doses

XI. Carcinomas - Dog

1. Carboplatin (Paraplatin®): 300 mg/m2, IV, Q/3-4 weeks

2. CMF protocol

5-Fluoruracil (5-FU® ): 150 mg/m2 BSA, IV, once a week;

Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, 4 days a week or QOD;

Methotrexate: 2.5 mg/m2 BSA, PO, 2 or 3 times a week.

3. FAC protocol

5-Fluoruracil (5-FU®): 150 mg/m2 BSA, IV, days 8 and 15

Doxorubicin (Adriamycin® ): 30 mg/m2 BSA, IV, day 1.

Cyclophosphamide (Cytoxan® ): 200-300 mg/m2 BSA, PO, day 10.

Sulfa-trimethoprim: 15 mg/kg, PO, BID

4. Cisplatin (Platinol®): 60-70 mg/m2 BSA, IV drip, Q/3 weeks. Prior intensive diuresis is required.

5. VAF protocol

Vincristine (Oncovin® ): 0.75 mg/m2 BSA, IV, days 8, 15;

Doxorubicin (Adriamycin® ): 30 mg/m2 BSA, IV, day 1;

5-Fluoruracil (5-FU® ): 150 mg/m2 BSA, IV, days 1, 8, 15.

6. VAC protocol

7. 5-Fluoruracil (5-FU®): 150 mg/m2 BSA, IV, once a week;

Cyclophosphamide (Cytoxan®): 50 mg/m2 BSA, PO, 4 days a week or QOD.

XII. Carcinomas - Cat

5-Fluoruracil is toxic for the cat, producing severe, and often fatal CNS signs. Cisplatin is also extremely toxic, causing acute pulmonary toxicity in this species.

1. Carboplatin (Paraplatin®) 200-240 mg/m2, IV, every 3-4 weeks.

2. AC protocol (28 day cycle)

Doxorubicin (Adriamycin® ): 1 mg/kg, IV day 1.

Cyclophosphamide (Cytoxan® ): 100-150 mg/m2 BSA on days 10 and 11.

3. VAC protocol (28 day cycle)

Vincristine (Oncovin® ): 0.5-0.75 mg/m2 BSA, IV, days 8, 15, 22.

Doxorubicin (Adriamycin® ): 1 mg/kg, IV day 1.

Cyclophosphamide (Cytoxan®): 100-150 mg/m2 BSA on days 10 and 11.

4. Vincristine (Oncovin® ): 0.5 mg/m2 BSA, IV, once a week.

Cyclophosphamide (Cytoxan® ): 50 mg/m2 BSA, PO, 4 days a week or QOD.

5. MiC protocol (21 day cycle):

Mitoxantrone (Novantrone®) 4-6 mg/m2 , IV drip over 4 hours, on day 1

Cyclophosphamide (Cytoxan®) 200-300 mg/m2 , PO, on day 10

6. MiCO protocol(21 day cycle):

Mitoxantrone (Novantrone®) 4-6 mg/m2 , IV drip over 4 hours, on day 1

Cyclophosphamide (Cytoxan®) 200-300 mg/m2 , PO, on day 10

Vincristine (Oncovin®) 0.5 to 0.6 mg/m2 , IV, on days 8 and 15

Neoadjuvant and Perioperative Therapy

It only takes 7-8 doublings after clinical detection for many types of cancers to become fatal. Therefore, I favor the concept of neoadjuvant (prior to surgery) and or perioperative chemotherapy. When a lymphoma patient has recovered fully from anesthesia, and is on IV fluids, I have administered an induction drug in divided doses over 24 hours. High-grade lymphoma has a relentless schedule of its own and does not wait two weeks for the patient to recover from surgery. Therefore, we need to finesse the art of medicine in these cases. We need to take courage and do what is best for the individual patient. This may go against the generalized staid textbook recommendations regarding healing times as being sacrosanct. If we view the surgery day as day 0, I like to give a 50% dose of vincristine on day one. If the patient is doing well, the other 50% of vincristine is given on day two. I will also give L-asparaginase at 400mg/m2 on either day one or day two, depending on the case. We hold off the use of prednisone until day 6 or 7 following surgery.

If a cancer patient is a candidate for radiation therapy (RTx), it is best to consult with the radiation oncologist before surgery and before ordering expensive diagnostic tests. Early referral may save the client money because the preliminary imaging used for the work up may favor CT over MRI. The radiation oncologist can set up the geriatric pet with diagnostic and therapeutic step-savers from the start. For instance, instead of ordering an MRI for a suspected brain tumor, if the owner is considering RTx, the medical oncologist would order a CT scan which is used by the radiation oncologist to interface with the radiation and dosimetry treatment plan. Another point to understand is that RTx can be safely started within a few days after surgery. The attending surgeon may be asked to mark the tumor field with clips so that the radiation oncologist has proper orientation. In many cases, RTx should be started as soon as possible after surgery despite the standard typical advice to "wait for two weeks" recommended by many attending surgeons. Every veterinary cancer, especially the geriatric patient, needs a team approach. All the doctors and specialists who work on the pet must strive to be in good communication with the oncologist. In this way, there will be fewer oversights and more efficient and beneficial patient care.

"Smart" Drugs

A new class of small molecule drugs designed to target tyrosine kinase in tumors are called "smart" drugs or stealth drugs. Gleevec™ (Imatinib, Mesylate) is a small molecule drug that inhibits a kinase in the abnormal Philadelphia chromosome found in chronic meylogenous leukemia CML) patients. Gleevec blocks the receptor tyrosine kinase (RTK) Kit at its ATP-binding site. Another small molecule drug, Erbitux, blocks the ability of cancer cells to absorb growth factors. Avastin is a small molecule drug that thwarts angiogenesis. Other small molecule inhibitors of kinases that are potentially useful against cancer are: Tarceva, Iressa, Cetuximab, Astra, Erptinob, Bevacizumab, etc.

SU11654 is a small molecule drug developed by Pfizer specifically as a veterinary product. It is an intracellular competitive inhibitor of ATP at the RTK domain. It causes tumor regression and inhibition of cell growth by inducing cell cycle arrest and apoptosis. This drug has efficacy against various tumors. Dogs with mast cell tumors treated with SU11654 had response rates that ranged up to 55% (London et al 2004). The long term efficacy, side effects, dose scheduling and maintenance costs are factors that will affect how veterinarians incorporate these new smart drugs into the contemporary management of geriatric cancer patients.

Proteonomics technology is a new and exciting technology which may not be very far off for practical applications in veterinary oncology. Our clients will be reading about SU11654 and other small molecule drugs for targeted therapy on the Internet and in lifestyle magazines. They will know that this class of drugs has broad efficacy against cancer, especially against mast cell tumors, because marketing to the public is the norm with big pharmaceutical companies. It all boils down to practical usefulness for our patients. If the drugs have tolerable side effects and can be made affordable, people will want them for their pet's survival. Cancer cells have dysregulated cell signaling which become targets for the new therapy agents using small molecules. These agents should be incorporated into the contemporary veterinarian's multimodality approach toward the treatment of cancer.

References and Resources

BSAVA Manual of Canine and Feline Oncology, eds., Dobson & Lascelles, British Small Animal Association, 2003.

Cancer in Dogs and Cats, Medical and Surgical Management, ed., Morrison, W.B., Teton New Media, 2002

Canine and Feline Geriatric Oncology: Honoring the Human-Animal Bond, Villalobos, A., Blackwell Publishing, 2007.

Comprehensive Geriatric Oncology, eds., Balducci, Lyman, William, Ershler, Martine, Exterman, Taylor & Francis, 2nd Ed., September 2004.

Crow, S.E., Chemoimmunotherapy for Canine Lymphoma Tumor Vaccines and Monoclonal Antibodies (1974-1994), www.cancer-therapy.org, Theilen Tribute Symposium Proceedings, Vol. 6A, 2008.

Feline Oncology, Ogilvie & Moore, Veterinary Learning Systems, 2001.

Jeglum, K.A., The history and future of canine lymphoma monoclonal antibody 231, www.cancer-therapy.org, Theilen Tribute Symposium Proceedings, Vol. 6A, 2008.

Lawman, M., Eidizadeh, S., Selmon, C., et al, Anti-tumor response induced by autologous cancer vaccine in canine lymphoma, www.cancer-therapy.org, Theilen Tribute Symposium Proceedings, Vol. 6A, 2008.

Managing the Veterinary Cancer Patient, Ogilvie & Moore, Veterinary Learning Systems, 1995.

Small Animal Clinical Oncology, eds., Withrow & MacEwen, 3rd Ed., Saunders, 2001.

Tumors in Domestic Animals, 3rd Ed., ed., Moulton, J. E., 1990, 4th Ed., ed., Meuten, D.J., Iowa State Press, 2002.

Veterinary Cancer Medicine, 2rd Ed., eds, Theilen & Madewell, Lea & Fibiger, 1987.

On line Resources

Veterinary Information Network (VIN) for interactive exhange of information.

www.veterinarypartner.com for VIN's client information tools

www.oncolink.upenn.edu./specialty./vet_onc for client information tools

www.vetmed.auburn.edu/distance/clinpath for diagnostic cytology information.

www.vetmed.lsu.edu/oncology for class notes provided by Dr. Neal Mauldin

veterinaryoncologyconsultants.com for clinician consults with Dr. Anthony Moore

www.gulfcoastvetspec.com/oncology/y2k/index.htm text by Dr. Kevin Hahn

http://pubmed.gov/ for full text biomedical articles dated back to 1966

clinicaltrials.gov accesses information on 5,000 mostly NIH clinical research studies

oncology.medscape.com provides current information on human oncology

www.perseusfoundation.org for pet loss and grief support for pet owners

www.deltasociety.org for pet loss support for pet owners

AOL Private Chat Room CRF, an online chat room for support of cats with chronic renal failure.