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Veterinary Pharmacology > Anti-Neoplastic Drugs > Flashcards

Anti-Neoplastic Drugs Flashcards

1
Q

What is cancer? Why is it difficult to treat?

A

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

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2
Q

What is a tumor? What is the difference between a benign and malignant tumor?

A

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

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3
Q

What are 5 causes of cancer in animals?

A
  1. genetics (mutations)
  2. environmental factors
  3. age
  4. viruses
  5. carcinogens from the environment, infection, and nutrition
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4
Q

What are 3 examples of viruses causing cancer?

A
  1. benign oral papilloma in the mouth of dogs
  2. canine transmissible venereal tumors
  3. FeLV
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5
Q

What are 4 known environmental hazards causing cancer in animals?

A
  1. UV radiation from the sun (melanoma)
  2. herbicides, insecticides, pesticides (lymphoma, leukemia)
  3. second-hand tobacco smoke (lung cancer, mesothelioma, ovarian cancer)
  4. air pollution and smog (lung cancer)
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6
Q

What is the incidence of cancer in animals? What is mortality like in dogs?

A

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

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7
Q

How does the incidence of cancer compare in dogs and cats?

A

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)

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8
Q

What is the difference between carcinoma, sarcoma, leukemia, and lymphoma?

A

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

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9
Q

What are the 5 most common types of cancer in dogs?

A
  1. mast cell tumors
  2. melanoma
  3. lymphoma
  4. osteosarcoma
  5. hemangiosarcoma
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10
Q

What are mast cell tumors? How are they graded?

A

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

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11
Q

What is the most common malignant tumor of a dog’s mouth?

A

melanoma

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12
Q

What is the most common bone tumor found in dogs? Where is it most commonly found?

A

osteosarcoma

larger breeds

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13
Q

What is hemangiosarcoma?

A

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

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14
Q

In what aged dogs is lymphoma most common? What 8 breeds?

A

middle-aged to older dogs

  1. Golden Retrievers
  2. Boxers
  3. Bullmastiffs
  4. Basset Hounds
  5. St. Bernards
  6. Scottish Terriers
  7. Airedale Terriers
  8. Bulldogs
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15
Q

What are 7 common signs of lymphoma in dogs?

A
  1. lethargy, inappetence
  2. swelling below the elbow or near the knee
  3. hard lumps under the skin
  4. difficulty breathing
  5. weight loss
  6. vomiting, diarrhea
  7. seizures
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16
Q

What are the 4 most common types of cancer in cats?

A
  1. lymphoma
  2. mammary (breast) cancer
  3. squamous cell carcinoma
  4. fibrosarcoma
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17
Q

What increases the risk of developing lymphosarcoma in cats?

A

feline leukemia virus infection - FeLV vaccines has decreased development

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18
Q

In what age of cats is mammary carcinoma most common? What can lower the chance of developing it?

A

older cats

spaying before the first heat cycle

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19
Q

What is the most common type of feline skin tumor? What does it usually involve? What is the most common locations?

A

squamous cell carcinoma

light and unpigmented skin —> sun exposure increases risk of developing SCC

hairless area of the nose, eyelids, and ears

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20
Q

What is fibrosarcoma?

A

aggressive tumor that develops from fibrous connective tissue

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21
Q

What are 5 common signs of FeLV infection? How is it spread?

A
  1. inappetence
  2. fever
  3. diarrhea
  4. inflammation of gums and mouth
  5. swollen lymph nodes

bite wounds, mutual grooming, sharing food dishes, litter boxes

22
Q

What is characteristic of most anticancer drugs?

A

sharp dose-response relationship and narrow therapeutic window (dose range of a drug that provides safe and effective therapy with minimal toxic side effects

23
Q

What are the 4 phases of clinical trials?

A

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

24
Q

Why do chemotherapies have serious side effects?

A
  • narrow therapeutic window
  • respond to damaged DNA, which is everywhere in the body
25
Q

What is the difference between neoadjuvant therapy and adjuvant therapy?

A

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

26
Q

What is palliation therapy?

A

treatment of clinical symptoms associated with metastasis

27
Q

What is the point of therapy given concurrently with radiation therapy?

A

increases tumor cell sensitivity to lethal effect of radiation

28
Q

What are the 4 types of cancer therapy?

A
  1. chemotherapy - alkylating agents, antimetabolites, plant alkaloids, antibiotics, topoisomerase inhibitors, corticosteroids
  2. targeted therapy - receptor and tyrosine kinase inhibitors, apoptosis-inducing agents, anti-angiogenic agents
  3. hormone therapy - hormone deprivation therapy, hormone receptor antagonists
  4. immunotherapy - monoclonal antibodies, checkpoint protein inhibitors, cancer vaccines
29
Q

What type of cancer therapy has fewer adverse effects? Why?

A

targeted therapy - small molecules and antibodies that target certain signaling pathways only exhibited by cancer cells

30
Q

What is the goal of chemotherapy in dogs? What happens with lymphoma that is not treated in this way?

A

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

31
Q

What 2 targeted therapies are approved for use in dogs?

A
  1. Palladia - anti-angiogenic and antiproliferative therapy used most commonly for mast cell tumors
  2. Laversia-CA1 - first small-molecule selective inhibitor of nuclear export (SINE) which targets and binds exportin-1 (XPO1) transported
32
Q

What is the first and only oral tablet to treat lymphoma in dogs?

A

Laversia-CA1

33
Q

What immunotherapy is used for dogs with osteosarcoma? What are 2 other common types?

A

vaccination and T-cell infusion (vaccine-primed adoptive cell therapy)

monoclonal antibodies, cancer vaccines

34
Q

What is the most common neoplasm in intact female dogs?

A

canine mammary tumors (CMTs)

35
Q

What 2 canine neoplasms are commonly treated with hormone therapy? What are they treated with?

A
  1. canine mammary tumors (CMTs) - tamoxifen with lots of side effects
  2. canine prostate cancer (BPH) - finasteride (hormone deprivation), flutamide (AR-agonist)
36
Q

What does the efficacy of chemotherapy in cats depend on? What are some common side effects?

A

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
37
Q

What targeted therapy is used in cats? How does it work?

A

Gleevac (imatinib) - binds and inhibits several protein-kinases in SCC

38
Q

What immunotherapy is used in cats? When is it most commonly used?

A

ALVAC IL-2 - helps cat’s immune system to kill any cancer cells that remain after surgery

39
Q

What kind of cancer common in dogs is less common in cats? Why?

A

prostate cancer

most cats are neutered, so prostate issues are less common

40
Q

How are most cancers treated?

A

single drugs at clinically tolerable doses have been unable to cure cancer - combination therapy

(initial success with hematologic malignancies)

41
Q

What are the 3 reasons for the use of combination therapy?

A
  1. provides maximal cell killing within the range of tolerated toxicity
  2. provides targeting of different signaling pathways in a heterogenous tumor population
  3. may prevent or slow the development of drug resistance
42
Q

What 5 principles should be considered when selecting the most effective combination of drugs for combination therapy?

A
  1. EFFICACY - only effective drugs when used alone against a tumor
  2. TOXICITY - toxicity of one drug should not overlap with toxicity of other drugs in the combination
  3. 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
  4. INTERACTION - clear understanding of how drugs in the combination can interact
  5. AVOID DOSE CHANGES - reducing the dose of one drug to add another into the combination can destroy drug effectiveness
43
Q

What is the goal of chemotherapy treatment? What is diagnosis based on?

A

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

44
Q

What do chemotherapy drugs target? What does this commonly associate them with? How does this compare between animals and humans?

A

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
45
Q

How are chemotherapy agents administered? Which way is preferred?

A
  • PO
  • IV
  • SQ
  • IM
  • IT

IV - 100% absorption

46
Q

Where are most chemotherapy agents metabolized and excreted? What does this lead to?

A

liver or kidney

toxic buildup in these organs causing dysfunction

47
Q

What is a persistent problem during the treatment of local and metastatic cancer?

A

development of chemoresistance

48
Q

How does chemoresistance occur? What are 5 mechanisms?

A

cancer cells that have been responding to therapy suddenly begin to grow

  1. cancer cells mutate
  2. gene amplification renders anticancer drug ineffective
  3. cancer cells learn to repair damaged DNA
  4. cancer cells develop a mechanism that inactivates the drug
  5. cancer cells pump the drug out of the cell as fast as it is going in using P-glycoprotein (MDR protein 1)
49
Q

What is P-glycoprotein (MDR protein 1)? How does it cause chemotherapy resistance?

A

functions as a biological barrier by extruding toxins and xenobiotics out of cells

cancer cells overexpress P-gp

50
Q

What 6 breeds of dogs are at higher risk of toxicity due to MDR1 gene mutation?

A
  1. Collie
  2. Border Collie
  3. Old English Sheepdog
  4. Longhaired Whippet
  5. Silken Windhound
  6. German Shepherd

Veterinary Pharmacology (35 decks)

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