1. Chemotherapy in Veterinary Medicine Presentation by Dominic Oliaro

2. Why I chose Veterinary Chemotherapy
I chose to present on veterinary chemotherapy because it’s a large area of interest to me and is very relevant to my field of work and study. Veterinary chemotherapy is a growing area of research and is largely in conjunction with human treatment. As a practicing veterinary technician I found this topic to be pretty interesting

3. What is Cancer?
Cancer is the unrestrained growth of cells that are damaged or destroy normal tissues and body parts
It is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues.
Cancer cells can spread to other parts of the body through the blood and lymph systems
Cancer types can be grouped into broader categories. The main categories of cancer include:
Carcinoma - cancer that begins in the skin or in tissues that line or cover internal organs.
Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.

4. What is Cancer Cont.
Lymphoma and myeloma - cancers that begin in the cells of the immune system
Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
Most cancers are believed to arise through a process called multistep carcinogenesis. There are three basic steps in multistep carcinogenesis:
(1)   Initiation: Initiating agents induce a permanent and irreversible change in the DNA of the affected cell. In and of itself, the initiating event is not significant to induce neoplastic transformation. Initiated cells cannot be distinguished from other cells in the surrounding environment.
(2)   Promotion: Promoting agents cause reversible tissue and cellular changes. Promoting agents can induce changes in cellular morphology, mitotic rate, and degree of terminal differentiation. Promotion serves to expand the initiated cell population and alter it in such a way as to increase the likelihood of another irreversible change occurring.

5. What is Cancer Cont. In order for a tumor to result:
(3)   Progression: Progressing agents are able to convert an initiated cell, or a cell undergoing promotion, into a cell exhibiting malignancy, capable of developing into a mature neoplasm. The process of progression is irreversible.
In order for a tumor to result:
The affected cell must be irreversibly altered at least twice.
The cell is altered once in the initiation phase and once in the progression phase
The promotion phase changes the affected cell in a way to increase the likelihood that the cell changed by the initiation will be in a position to be changed by the progression phase.

6. What is Cancer Cont.

7. Cancer Treatment
The three most common treatment options for cancer are:
Surgery
Surgery is useful to remove or minimized localized tumors.
Radiation therapy
Radiation therapy can be used alone, or in conjunction with surgery and chemotherapy, to treat local disease. Radiation therapy is most often used to treat smaller tumors.
Chemotherapy.
Chemotherapy is used treat cancer non invasively and systemically.

9. What is Chemotherapy?
Chemotherapy for animals is much different from that for human cancer patients
For animals receiving chemotherapy, quality-of-life and the basic goal of extension of life span for the patient is the primary concern
In many cases, doctor are unable to cure veterinary cancer patients. The goal, once again, is therefore to improve a pet's quality of life. To this end, chemotherapy can be used to minimize the discomfort caused by a tumor or to slow down the progression of the disease.
Doses of drugs and treatment schedules are calculated to minimize discomfort to the patient, while providing the most effective defense against the disease.

10. What is Chemotherapy cont.
Most people are pleasantly surprised at how well their pets feel while undergoing chemotherapy.
For most (but not all) types of tumors, the oncologist will provide information on average life expectancy with and without treatments
Although the word chemotherapy can mean the use of any drug to treat any disease, to most people chemotherapy refers to drugs used for cancer treatment

11. Mechanisms of Chemotherapy
The goal of chemotherapy is to inhibit the growth of cancer cells with minimum effect on normal cells
Most chemotherapeutic agents either bind directly to genetic material in the cell nucleus, or affect a cell's ability to synthesize protein, which may damage growth and reproduction of normal cells as well (and usually do).
Chemotherapeutic agents are classified according to their pharmacologic action, and the point in the cell cycle at which they interfere with cellular reproduction.
Cycle phase-specific: Drugs that are active only during a specific phase of the cell cycle
Cycle phase-nonspecific: Drugs that are active regardless of the cell cycle phase

12. Mechanisms of Chemotherapy Cont.
Following cell death, resting cells are 'awakened' into the reproduction cycle and are then more susceptible to chemotherapeutic agents
Regardless of the specific mechanism of the intracellular disruption, the cell will die as it attempts cell division if it is not capable of repairing itself.
The cell kill rate of various drugs is related to the concentration of the drug and to the degree of tumor cell exposure over time.
Combining cytotoxic drugs is an important, effective strategy in chemotherapy, because when drugs are used in combination, they often enhance the activities of each other

13. History of Chemotherapy
The first drug used for cancer chemotherapy did not start out as a medicine
Mustard gas was used as a chemical warfare agent during World War I and was studied further during World War II.
During a military operation in World War II, a group of people were accidentally exposed to mustard gas and were later found to have very low white blood cell counts.
Doctors reasoned that something that damaged the rapidly growing white blood cells might have a similar effect on cancer.
In the 1940s, several patients with advanced lymphomas (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas. Their improvement, although temporary, was remarkable.

14. History of Chemotherapy Cont.
The experience with mustard gas led researchers to look for other substances that might have similar effects against cancer and as a result, many other drugs have been developed.
The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers facilitated the study of adjuvant chemotherapy
Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

15. Administration
Treatment dose and schedule depends on the type of cancer and chemotherapy method.
In many cases periodic chemotherapy will be necessary to control the cancer for the rest of the pet's life.
For maximum therapeutic effect, a drug should be used with a dose that causes minimal toxicity with maximal effectiveness. The most effective dose of chemotherapeutic agents is often very close to the toxic dose.
Doses of chemotherapeutic agents are often calculated on the basis of body surface area in square meters, rather than by a patient's weight.
The following charts give some common dosages for many drugs and the conversion chart used for dogs and cats

18. Administration cont.
The duration of chemotherapy depends on the type of cancer and the extent of disease
Some animals need to receive chemotherapy for the rest of their lives.
In others, treatments may be spread out or discontinued after a period of weeks to months provided that the cancer is in remission

19. Drugs
Prednisone is the least toxic of all the chemotherapy agents. It is not a specific chemotherapy drug, and has many different uses in medicine. It is usually well tolerated by pets. It commonly causes increased thirst, urinations, and appetite. It can have irritating effects on the stomach lining.
Elspar (Asparaginase) is also well tolerated. In rare instances, it can cause vomiting due to pancreatitis. Since it is a protein, there is a (rare) possibility that an animal can have an allergic reaction to it.
Vincristine has little tendency to make an animal ill. Occasionally, there will be 1 or 2 episodes of "innocuous" vomiting 24 hours after the injection, which disappears without treatment. It is very irritating to the surrounding tissues if it leaks from the vein at the injection site.

20. Drugs Cont.
Cytoxan is a potent chemotherapeutic agent and can lower the white blood cell count about 7 days after it is given. Occasionally, bloody urine can occur due to bladder effects.
Adriamycin is the most potent of the agents, and like Cytoxan, can lower the white blood cell count. Long term effects can involve the heart, but protocols have been calculated to lower this risk.
Most of the drugs are excreted in the urine within about 48 hours after administration.

21. Side Effects
Practically all anticancer drugs have side effects. However, their potential effect against the cancer generally outweighs the possible side effects.
Compared to people who receive chemotherapy, pet animals experience fewer and less severe side effects because lower doses of drugs are used and are not combined as many drugs in human medicine are.
Below are listed some potential side effects of many chemotherapeutic agents:
Hair Loss (Alopecia)-Animals rarely lose their hair, but if they do, they are not bothered by it as much as people are. In most pet animals, hair does not grow continually throughout their lives like it does in people. Therefore, hair loss in pets is rare.
Loss of White Blood Cells (Neutropenia)-Many chemotherapeutic agents impair the bone marrow's ability to produce cells. As a result, neutropenia may occur seven to ten days after chemotherapy. Neutropenia, alone, is not a danger to a patient. However, a patient's ability to fight off infection is impaired by neutropenia.

22. Side Effects Cont.
Stomach or Intestinal (Gastrointestinal) Discomfort-Many patients experience some form of stomach or intestinal discomfort two to seven days after a chemotherapy treatment.
Tissue Damage-If some chemotherapy agents are accidentally given outside the vein, severe tissue reactions can result.
Allergic Reactions-Allergic reaction to chemotherapeutic agents is rare, and if there is a reaction it develops upon initial administration and is treated quickly.
Heart Damage-Some chemotherapeutic agents, in some rare cases, can irreversibly damage the heart muscle. The dose of these agents prescribed for is below the dose that usually causes heart disease.

23. Costs & Commitment
For a cancer such as lymphoma, therapy involves a significant time commitment on the part of the owner/family.
Outpatient visits are generally once weekly for 4 weeks, then every 3 weeks for up to 18 months
Relative to most other treatments in veterinary medicine, chemotherapy is a costly service to provide:
The costs reflect the professional time and expertise required
The high costs of chemotherapy agents (the same used by humans)
The special equipment and personnel protection required
The removal of biomedical hazard waste

24. Is it Worth it?
Costs can be very high as well as commitment and time dedicated to the treatment.
Quality of life can be extended
The goal of veterinary chemotherapy in pets is palliation, and is not a rigorous, painful process that aims to cure the cancer, as in human medicine.
Every situation and client-pet relationship is different and is usually dealt with individually.
Most animals do indeed appear to enjoy their extended life period and do not even realize that they are “ill”.
It really comes down to if the client can pay for it or is willing to pay to comfort and extend the life of their animal.

25. Conclusions
In every veterinary hospital, the most important goal of cancer therapy must be maintaining the pet's quality of life
Currently, treatment of cancer in animals can often result in fairly lengthy, good quality remission times. That still means that for many types of cancers, their return is inevitable.
The ultimate goal of therapy would be to cure the patient of cancer. In most instances at this point in time in veterinary medicine, this goal is not realistic.

26. Conclusions
The goal is to control rapid progression of the disease, prevent spread of the tumor, restore deteriorated function, and provide a good quality of life during the time of remission.
The decision of whether to pursue chemotherapy treatments can be complex.
Medical information, practical concerns (such as need for repeated visits, the animals temperament, etc.), and financial responsibility all play a part in this decision.

27. References
Morrison, W.B Cancer Chemotherapy: An Annotated History. Journal of Veterinary Internal Medicine. Vol. 24 Issue 6:
Crump, Kenneth Veterinary Oncology: Cancer and Chemotherapy. Veterinary Support Personnel Networkhttp:// Retrieved April 2012
Withrow SJ, MacEwen, EG: Small Animal Clinical Oncology, Second Edition. WB Saunders Company.
Goodman, MS: Cancer: Chemotherapy and Care. 1986, Bristol-Myers Oncology Division.
McCurnin DM: Clinical Textbook for Veterinary Technicians, Fourth Edition. WB Saunders Company.
O'Brien, MG: Cancer pain management: a review of recent considerations and advancements. Veterinary Cancer Society Newsletter, Vol 22. No.2, Summer 1998.
Chemotherapy and cytotoxic drug safety plan. Veterinary Support Personnel Network, (URL):