Anti-Neoplastic Drugs Flashcards
What is cancer? Why is it difficult to treat?
group of diseases involving uncontrolled growth of abnormal cells with the potential to invade or spread to other parts of the body through the blood and lymphatics
cannot treat metastasis yet
What is a tumor? What is the difference between a benign and malignant tumor?
neoplasm - abnormal mass of tissue that results when cells divide more than they should or do not die when they should
BENIGN = tumor grows larger but does not invade/spread
MALIGNANT = cancer; has potential to invade and destroy nearby tissues and spread to other parts of the body
What are 5 causes of cancer in animals?
- genetics (mutations)
- environmental factors
- age
- viruses
- carcinogens from the environment, infection, and nutrition
What are 3 examples of viruses causing cancer?
- benign oral papilloma in the mouth of dogs
- canine transmissible venereal tumors
- FeLV
What are 4 known environmental hazards causing cancer in animals?
- UV radiation from the sun (melanoma)
- herbicides, insecticides, pesticides (lymphoma, leukemia)
- second-hand tobacco smoke (lung cancer, mesothelioma, ovarian cancer)
- air pollution and smog (lung cancer)
What is the incidence of cancer in animals? What is mortality like in dogs?
6 million new cancer diagnoses made in dogs and cats each year
45% of dogs 10 years of age or older and 23% of dogs of all ages died of cancer, making it a leading cause of death
How does the incidence of cancer compare in dogs and cats?
dogs get cancer approximately at the same rate of humans (cause of death in 50% of dogs over 10 years old)
the incidence in cats is slightly lower (cause of death in 33% of cats regardless of age)
What is the difference between carcinoma, sarcoma, leukemia, and lymphoma?
CARCINOMA - cancer that begins in the skin or in tissues that line of cover internal organs (breast, lung, prostate)
SARCOMA - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective and supportive tissues
LEUKEMIA - cancer that starts in blood-forming tissue, such as bone marrow, and causes large numbers of blood cells to be produced and enter the blood
LYMPHOMA - cancer affecting the immune system, mostly lymphocytes in the lymph nodes, spleen, liver, GI tract, and bone marrow
What are the 5 most common types of cancer in dogs?
- mast cell tumors
- melanoma
- lymphoma
- osteosarcoma
- hemangiosarcoma
What are mast cell tumors? How are they graded?
form of skin cancer of mast cells that reside in connective tissue, especially the vessels and nerves close to the external surface of the skin, lungs, nose, and mouth
location in the skin, presence of inflammation, differentiation
What is the most common malignant tumor of a dog’s mouth?
melanoma
What is the most common bone tumor found in dogs? Where is it most commonly found?
osteosarcoma
larger breeds
What is hemangiosarcoma?
highly malignant cancer that can spread rapidly, causing tumors almost everywhere in the body mostly in the heart and spleen - tends to be in the advanced stage before it is diagnosed
In what aged dogs is lymphoma most common? What 8 breeds?
middle-aged to older dogs
- Golden Retrievers
- Boxers
- Bullmastiffs
- Basset Hounds
- St. Bernards
- Scottish Terriers
- Airedale Terriers
- Bulldogs
What are 7 common signs of lymphoma in dogs?
- lethargy, inappetence
- swelling below the elbow or near the knee
- hard lumps under the skin
- difficulty breathing
- weight loss
- vomiting, diarrhea
- seizures
What are the 4 most common types of cancer in cats?
- lymphoma
- mammary (breast) cancer
- squamous cell carcinoma
- fibrosarcoma
What increases the risk of developing lymphosarcoma in cats?
feline leukemia virus infection - FeLV vaccines has decreased development
In what age of cats is mammary carcinoma most common? What can lower the chance of developing it?
older cats
spaying before the first heat cycle
What is the most common type of feline skin tumor? What does it usually involve? What is the most common locations?
squamous cell carcinoma
light and unpigmented skin —> sun exposure increases risk of developing SCC
hairless area of the nose, eyelids, and ears
What is fibrosarcoma?
aggressive tumor that develops from fibrous connective tissue
What are 5 common signs of FeLV infection? How is it spread?
- inappetence
- fever
- diarrhea
- inflammation of gums and mouth
- swollen lymph nodes
bite wounds, mutual grooming, sharing food dishes, litter boxes
What is characteristic of most anticancer drugs?
sharp dose-response relationship and narrow therapeutic window (dose range of a drug that provides safe and effective therapy with minimal toxic side effects
What are the 4 phases of clinical trials?
I - candidate drug is tested in various doses to establish toxicity dose (maximum tolerated dose)
II - larger group of cancer patients for certain type of cancer and stage of tumor progression
III - patients with refractory disease
IV - comparison of newly introduced drug to other drugs used in clinic for similar cancer
Why do chemotherapies have serious side effects?
- narrow therapeutic window
- respond to damaged DNA, which is everywhere in the body
What is the difference between neoadjuvant therapy and adjuvant therapy?
NEOADJUVANT = (induction therapy) treatment given as a first step to shrink a tumor before main treatment (surgery), since large tumor surgery is difficult and has a high risk of missing all cancerous cells, allowing for recurrence
ADJUVANT = treatment given after surgery to kill any remaining cancer cells with the goal of reducing chances of recurrence and metastasis
What is palliation therapy?
treatment of clinical symptoms associated with metastasis
What is the point of therapy given concurrently with radiation therapy?
increases tumor cell sensitivity to lethal effect of radiation
What are the 4 types of cancer therapy?
- chemotherapy - alkylating agents, antimetabolites, plant alkaloids, antibiotics, topoisomerase inhibitors, corticosteroids
- targeted therapy - receptor and tyrosine kinase inhibitors, apoptosis-inducing agents, anti-angiogenic agents
- hormone therapy - hormone deprivation therapy, hormone receptor antagonists
- immunotherapy - monoclonal antibodies, checkpoint protein inhibitors, cancer vaccines
What type of cancer therapy has fewer adverse effects? Why?
targeted therapy - small molecules and antibodies that target certain signaling pathways only exhibited by cancer cells
What is the goal of chemotherapy in dogs? What happens with lymphoma that is not treated in this way?
dog will not be cured, but may have its life prolonged for 2-24 months —> dog can feel better, still suffer from cancer, or suffer side effects from treatment
life expectancy is only 1-2 months —> with treatment, reach remission with an average survival of 12-14 months
What 2 targeted therapies are approved for use in dogs?
- Palladia - anti-angiogenic and antiproliferative therapy used most commonly for mast cell tumors
- Laversia-CA1 - first small-molecule selective inhibitor of nuclear export (SINE) which targets and binds exportin-1 (XPO1) transported
What is the first and only oral tablet to treat lymphoma in dogs?
Laversia-CA1
What immunotherapy is used for dogs with osteosarcoma? What are 2 other common types?
vaccination and T-cell infusion (vaccine-primed adoptive cell therapy)
monoclonal antibodies, cancer vaccines
What is the most common neoplasm in intact female dogs?
canine mammary tumors (CMTs)
What 2 canine neoplasms are commonly treated with hormone therapy? What are they treated with?
- canine mammary tumors (CMTs) - tamoxifen with lots of side effects
- canine prostate cancer (BPH) - finasteride (hormone deprivation), flutamide (AR-agonist)
What does the efficacy of chemotherapy in cats depend on? What are some common side effects?
type of cancer, stage of cancer, how feline’s body reacts to the drugs —> stage 1 and 2 = positive prognosis; stage 3 and 4 = poor prognosis
- nausea
- vomiting
- lethargy
- constipation
- abnormally dark urine
What targeted therapy is used in cats? How does it work?
Gleevac (imatinib) - binds and inhibits several protein-kinases in SCC
What immunotherapy is used in cats? When is it most commonly used?
ALVAC IL-2 - helps cat’s immune system to kill any cancer cells that remain after surgery
What kind of cancer common in dogs is less common in cats? Why?
prostate cancer
most cats are neutered, so prostate issues are less common
How are most cancers treated?
single drugs at clinically tolerable doses have been unable to cure cancer - combination therapy
(initial success with hematologic malignancies)
What are the 3 reasons for the use of combination therapy?
- provides maximal cell killing within the range of tolerated toxicity
- provides targeting of different signaling pathways in a heterogenous tumor population
- may prevent or slow the development of drug resistance
What 5 principles should be considered when selecting the most effective combination of drugs for combination therapy?
- EFFICACY - only effective drugs when used alone against a tumor
- TOXICITY - toxicity of one drug should not overlap with toxicity of other drugs in the combination
- OPTIMUM SCHEDULING - drugs in combination should be able to be given at consistent intervals and treatment-free interval should be shortest time necessary for bone marrow recovery
- INTERACTION - clear understanding of how drugs in the combination can interact
- AVOID DOSE CHANGES - reducing the dose of one drug to add another into the combination can destroy drug effectiveness
What is the goal of chemotherapy treatment? What is diagnosis based on?
extend life with an improved quality of life through palliation of clinical signs and induction of only microscopic disease with incomplete tumor control
accurate diagnosis and determination of clinical stage
What do chemotherapy drugs target? What does this commonly associate them with? How does this compare between animals and humans?
not only cancer cells, but those that rapidly divide, like gonads, hair, skin, and GI tract
side effects like myelosuppression, reduced fertility, loss of hair, mouth ulcers, and diarrhea
- hair loss is rare in animals
- animals experience fewer and less severe side effects due to lower doses of drugs and combination of less drugs
How are chemotherapy agents administered? Which way is preferred?
- PO
- IV
- SQ
- IM
- IT
IV - 100% absorption
Where are most chemotherapy agents metabolized and excreted? What does this lead to?
liver or kidney
toxic buildup in these organs causing dysfunction
What is a persistent problem during the treatment of local and metastatic cancer?
development of chemoresistance
How does chemoresistance occur? What are 5 mechanisms?
cancer cells that have been responding to therapy suddenly begin to grow
- cancer cells mutate
- gene amplification renders anticancer drug ineffective
- cancer cells learn to repair damaged DNA
- cancer cells develop a mechanism that inactivates the drug
- cancer cells pump the drug out of the cell as fast as it is going in using P-glycoprotein (MDR protein 1)
What is P-glycoprotein (MDR protein 1)? How does it cause chemotherapy resistance?
functions as a biological barrier by extruding toxins and xenobiotics out of cells
cancer cells overexpress P-gp
What 6 breeds of dogs are at higher risk of toxicity due to MDR1 gene mutation?
- Collie
- Border Collie
- Old English Sheepdog
- Longhaired Whippet
- Silken Windhound
- German Shepherd
