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Pharmacology II > Anti-Neoplastics #1 > Flashcards

Anti-Neoplastics #1 Flashcards

1
Q

Define cancer.

A

Cancer is a group of diseases involving uncontrolled growth of abnormal cells with the potential to invade or spread to other parts of the body (metastasis).

We are unable to treat metastasis. We can help people live longer but not treat this.

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2
Q

What is the difference between benign and malignant tumors?

A

These contrast with benign tumors, which do not spread.

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3
Q

What is the definition of a tumor?

A

Tumor (Neoplasm): An abnormal mass of tissue that results when cells divide more
than they should, or do not die when they should.

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4
Q

Malignant (cancer) tumors have the potential to?

A

invade and destroy nearby tissues and
spread to other parts of the body

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5
Q

Benign tumors may?

A

may grow larger but does not invade/spread

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6
Q

What causes cancer in animals?

A

❖ Genetic Factors (genetic mutations –> cancer)
❖ Environmental factors
❖ Age (some cancers, e.g. prostate cancer is an age-related cancer. rarely affected younger individuals, except genetic)
❖ Viruses: oral papilloma in the mouth of dogs (benign);
genital cancer of dogs (canine transmissible venereal tumor)]
feline leukemia virus, in 30% cats
❖ Carcinogens (environmental, infectious, and nutrition & dietary). most dog food today is hard to digest, not getting nutrients they need. most digestion takes place in the stomach. caffeine and theobromide = carcinogenic to dogs

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7
Q

What are the known environmental factords that cause cancer?

A

UV radiation = melanoma and squamous skin cell carcinoma

Tobacco smoke = lung cancer, mesothelioma,

Air pollution and smog in urban areas

Variety of herbicides, insecticides, and pesticides
commonly used in agriculture = lymphoma, leukemia, prostate cancer

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8
Q

According to the Comparative Oncology Program of the U.S. National Cancer Institute, there are ___ million pet dogs and ___ million pet cats in the United States. Approximately ___ million new cancer diagnoses are made in dogs and the same number made in cats each year

A

65, 32, 6

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9
Q

45% of dogs ____ years of age or older and 23% of dogs of ___ ages died of cancer, making it a leading cause of death in this species. The overall estimated incidence of malignant neoplasia in companion animals reportedly ranges from approximately ___ to ___ per 100,000 dogs

A

10, all, 381, 852

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10
Q

T/F: Cancer is not one of the most common causes of death and debilitating illness in both dogs and cats

A

False, it is.

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11
Q

_____ get cancer approximately at the same rate as humans, while the incidence in ____ is slightly lower

A

Dogs, cats

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12
Q

Many other species get cancer, but we don’t have any reliable statistics for them

A
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13
Q

Cancer is estimated to be the cause of death in 50% of dogs over the age of ____

A

10

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14
Q

Cancer is the cause of death in approximately _____% of cats, regardless of age

A

33

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15
Q

Define carcinoma.

A

Carcinoma: a cancer that begins in the skin or in tissues that line or cover internal organs (breast, lung, prostate)

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16
Q

Define sarcoma.

A

Sarcoma: a cancer that begins in bone, cartilage, fat, muscle, blood
vessels, or other connective and supportive tissues (osteosarcoma - very prevalent in dogs)

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17
Q

Define leukemia.

A

Leukemia: a cancer that starts in blood-forming tissue, such as the bone marrow, and causes large numbers of blood cells to be produced and enter
the blood

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18
Q

Define lymphoma.

A

Lymphoma: a cancer affecting immune system, mostly lymphocytes in the
lymph nodes. Hodgkin’s lymphoma and non-Hodgkin lymphoma

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19
Q

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

A
  1. Mast cell tumors
  2. Melanoma
  3. Lymphoma
  4. Osteosarcoma
  5. Hemangiosarcoma
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20
Q

Define mast cell tumors.
How are they graded?

A

Mast Cell Tumors are a form of skin cancer. Mast cells are cells that reside in the connective
tissues, especially the vessels and nerves that are close to the external surface of dog’s skin, lungs, nose, and mouth. Mast cell tumors are graded according to their location in the skin, presence of inflammation and how well they are differentiated

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21
Q
  1. Melanoma is a common type of cancer in which species?
  2. Melanoma is the most common malignant tumor in which species? In which part of the body?
  3. Skin tumors are among the most common tumors in which species? Are they benign or malignant?
A
  1. Melanoma is a common type of cancer in dogs.
  2. Most common malignant tumor of a dog’s mouth.
  3. Skin tumors are among the most common tumors found in dogs and many are benign
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22
Q

Define lymphoma.

A

Lymphoma is a cancer of lymphocytes and lymphoid tissues. Lymphoid tissue is normally present in many places in the body, including lymph nodes, spleen, liver, GI tract and bone
marrow

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23
Q

Define osteosarcoma.

A

Osteosarcoma refers to the most common bone tumor found in dogs. Bone cancer can affect any breed of dog, but it is more commonly found in the larger breeds

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24
Q

Define hemangiosarcoma.

A

Hemangiosarcoma is a highly malignant cancer that can spread rapidly, causing tumors almost anywhere in the body. It is most often found in the dog’s heart and spleen. Many times, it is in the advanced stage before it is diagnosed

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25
Q

Define Primary lung cancer in dogs.

A

Has not metastasized yet.

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26
Q

Define metastatic lung cancer.

A
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27
Q

Define hemangiosarcoma.

A
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28
Q

Define squamous cell carcinoma.
What part of the body is affected?
How do they heal?

A

See below

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29
Q

What it the most common form of skin cancer in dogs?

A

MCT

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30
Q
  1. Lymphoma accounts for what % of cancer in dogs?
  2. What part of the body is affected?
  3. What is the most effective form of treatmet?
A

See below

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31
Q
  1. Is osteosarcoma common or uncommon?
  2. Is this an aggressive or non-aggressive form of cancer? Does this cancer metastasize? Or not so much?
A

See below

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32
Q
  1. Lymphoma is what type of cancer?
  2. What part of the body is affected?
A

See below

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33
Q

What is the main cause of lymphoma?

A

See below

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34
Q

What are signs of cancer in a dog?

A

See below

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35
Q

Cancer is most common in which dog breeds?

A

It is most common in middle-aged and older dogs, and some breeds are predisposed. Golden Retrievers, Boxer Dogs, Bullmastiffs, Basset Hounds, Saint Bernards, Scottish Terriers, Airedale Terriers, and
Bulldogs all appear to be at increased risk of developing lymphoma.

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36
Q

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

A
  1. Lymphoma
  2. Feline Leukemia Virus (FeLV)
  3. Mammary (breast) cancer
  4. Skin cancer (squamous cell carcinoma)
  5. Fibrosarcoma
37
Q

Define lymphoma in cats.
The age of affected cats?
What increases the risk of developing lymphosarcoma?

A

Lymphoma is a cancer of lymphocytes and lymphoid tissues. Lymphoid tissue is normally
present in many places in the body, including GI tract, the chest structure, the liver, spleen, and
kidneys. The age of affected cats ranges, on average, from 2 to 6 years. Infection with the
feline leukemia virus increases the risk of developing lymphosarcoma

38
Q

FeLV was one of the leading causes of?

A

Feline Leukemia Virus (FeLV) was one of the leading causes of lymphoma in cats until the
development of the FeLV vaccine

39
Q
  1. Mammary cancer tends to develop in cats of what age group?
  2. What will lessen the risk of a cat developing mammary cancer?
  3. Is mammary cancer in male cats common or uncommon?
A

Mammary (breast) Cancer tend to develop in older cats. Spaying cats before their first heat lessen the risk of future mammary tumor development. It is rare for male cats to be affected with mammary cancer

40
Q

SCC accounts for what % of feline skin tumors?
What part of the body is affected?

A
  1. Skin Cancer (squamous cell carcinoma) accounts for a high percentage of all feline skin tumors.
  2. These tumors usually involve light or un-pigmented skin, and sun exposure increases
    the risk of a cat developing SCC. The most common locations are the hairless area of the nose, the eyelids, and ears
41
Q

Define fibrosarcoma

A

Fibrosarcoma is an aggressive tumor that develops from fibrous connective tissue

42
Q
  1. What % of cats die from cancer?
  2. How many cats are affected by cancer each year?
A
  1. 32
  2. 6 million
43
Q

Name the most common forms of lymphoma/lymphosarcoma in cats

A
  1. Renal
  2. GI
  3. Nasal
  4. Spinal
  5. Mediastinal LN
  6. Multicentric
44
Q
  1. What happens as a result of FeLV?
  2. What happens if FeLv is left untreated?
  3. What are the clinical signs of FeLV in cats?
  4. How is FeLV transmitted?
A
  1. Increases susceptible to infection/other diseases.
  2. If left untreated, FeLV+ cats will develop cancer or blood disorder
  3. Fever, loss of appetite, diarrhea, swollen LN, inflammation of the gums and around the mouth.
  4. Bite wounds, mutual grooming, sharing food bowls and litter boxes
45
Q

What are the possible causes of cancer in cats?

A
46
Q

Most anticancer drugs are characterized by ?

A

a sharp dose-response relationship
and narrow therapeutic window.

47
Q

What defines the therapeutic window?

A

Measurements of PD, taken together with studies of PK and toxicity, define the
Therapeutic Window in which a drug should be given – the dose range of a drug
that provides safe and effective therapy with minimal toxic side effects.

48
Q
A

Low dose of drugs tend ot not be effective, hence why we use high doses. but high doses come with side effects.

49
Q

Define phase I of clinical trials.

A

Phase I: candidate drug is tested in various doses to establish
toxicity dose (MTD

50
Q

Define phase II of clinical trials.

A

Phase II: Larger group of cancer patients for certain type of
cancer and for certain stage of tumor progression

51
Q

Define phase III of clinical trials

A

Phase III: patients with refractory disease

52
Q

Define phase IV of clinical trials

A

Phase VI: comparison of a newly introduced drug to other drugs
used in clinic for similar cancer

53
Q

Define neoadjuvant therapy.

A

Neoadjuvant therapy: treatment given as a first step to shrink a tumor
before the main treatment, which is usually surgery

Doing surgery on a large tumor is not only difficult but also increases risk of metastasis b/c some cells can escape/you may not remove all of it.

54
Q

Define adjuvant therapy.

A

Adjuvant therapy: treatment given after surgery to kill any remaining cancer cells
with the goal of reducing the chances of recurrence and metastasis

55
Q

Define palliation therapy.

A

Palliation therapy: of clinical symptoms associated with metastasis. Nothing can be done in this case, so this is essentially hospice.

56
Q

Drug therapy can also be given concurrently with radiation therapy to?

A

Increase tumor cell sensitivity to the lethal effect of radiation therapy.

57
Q

What are the different types of cancer therapy?

A
  1. Chemotherapy
  2. Targeted therapy
  3. Hormone therapy
  4. Immunotherapy
58
Q

What are the different types of chemotherapy?

A

❑ Alkylating Agents
❑ Antimetabolites
❑ Plant Alkaloids
❑ Antibiotics
❑ Topoisomerase Inhibitors
❑ Corticosteroids

IM, SC, IV, or directly into tumor, oral tablets

Administered by oncologists only.

59
Q

What are the different types of targeted therapy?

A

small molecules and antibodies
❑ Receptor & Tyrosine Kinase Inhibitors
❑ Apoptosis-inducing Agents
❑ Anti-Angiogenic Agents

Trying to target tumor while not damaging normal, healthy cells. This is less adverse than chemotherapy.

60
Q

What are the different types of hormone therapy?

A

❑ Hormone deprivation therapy
❑ Hormone receptor antagonists

61
Q

What are the different types of immunotherapy?

A

❑ Monoclonal Antibodies
❑ Checkpoint protein inhibitors
❑ Cancer vaccines

Lots of side effects

62
Q

Chemotherapy for dogs

A

The dog will not be cured by chemotherapy but may have its life prolonged from 2–24 months. The dog may feel better, still suffering from the cancer, or it may suffer from the side effects of the treatment. Untreated dogs have an average survival time of 4–6 weeks

Without treatment the life expectancy in dogs with lymphoma is 1-2 months. With
treatment, in dogs that feel well, about 80% – 90% of dogs with lymphoma attain a complete
remission with an average survival of 12-14 months

63
Q

Name the two forms of targeted therapy for dogs.

A

Targeted therapy for dogs: (approved in Vet Med)
PalladiaR (toceranib phosphate): anti-angiogenic and antiproliferative therapy specifically for dogs (mast cell tumors)
Laversia-CA1R (verdinexor): is the first small-molecule selective inhibitor of nuclear export (SINE),
which targets and binds to Exportin-1 (XPO1) transporter. It is the first and ONLY oral tablet to treat lymphoma in dogs

64
Q
  1. Name an example of immunotherapy for dogs that treats osteosarcoma.
  2. What other forms of immunotherapy are used to treat cancer in dogs?
A
  1. Vaccination and T-cell infusion (vaccine-primed Adoptive Cell Therapy) in dogs with osteosarcoma.
  2. Monoclonal antibodies, cancer vaccines
65
Q
  1. What is the most common neoplasm in intact female dogs?
  2. What medication is used to treat human BC? Is this drug used in vet med?
  3. Have Aromatase inhibitors been used in vet med?
  4. What forms of hormone therapy have been used to treat Canine prostate cancer (BPH).
A
  1. Canine mammary tumors (CMTs) is the most common neoplasm in intact female dogs.
  2. Tamoxifen is utilized in the treatment of human BC. (lot of side effects in CMT).
  3. No clinical trials in dogs.
  4. Hormone deprivation therapy (Finasteride) and AR-antagonist (Flutamide)
66
Q
  1. The efficacy of chemotherapy in cats depends on?
  2. Felines that have stage 1 or stage 2 cancer types have a what type of prognosis? Stage 3 and 4?
  3. What are the side effects of cancer in cats?
A
  1. The type of cancer, the stage of cancer, and how the feline’s body reacts to the cancer drugs.
  2. Positive prognosis for a full recovery, whereas stage 3 and 4 type cancers have a poor prognosis
  3. Side effects: nausea, vomiting, tiredness, constipation, and abnormally dark urine coloration
67
Q

Name the targeted therapy used to treet SCC in cats. What is their function?

A

Targeted therapy in cats:
Gleevac (imatinib) is used in cats (off label): binds and inhibits several protein-tyrosine kinases in squamous cell carcinoma

68
Q

ALVAC IL-2 is a type of ___________. It is an ________ designed to help a cat’s immune system to kill any cancer cells that ______ following surgery.

A

immunotherapy, injection, remain

69
Q

❖ Hormone therapy for cats:

A mammary (breast) tumor is a common tumor in cats, can _________.
Prostate cancer are _____ in cats (Most cats are _________ so that may be one reason prostate issues are ____ common)

A

metastasize, rare, neutered, less

70
Q

What is combination therapy? What are the pros and cons?

A

Combination Therapy
▪ With rare exceptions, single drugs at clinically tolerable doses have been unable to
cure cancer
▪ In late 1960-early 70s drug combination regimens were developed based on the
known biochemical actions rather than on their clinical efficacy (Not effective)
▪ Initial success was achieved with hematologic malignancies using drugs from different
classes, after which combination chemotherapy was extended to the treatment of solid tumors

71
Q

Reasons for the use of combination therapy

A

▪ Provides maximal cell kill within the range of tolerated toxicity
▪ Provides targeting of different signaling pathways in a heterogeneous tumor
population. More efficient to target more than one pathway that impact the growth of tumor. Side effects with this as well.
▪ It may prevent or slow the development of drug resistance. If patient develops resistance to one drug, maybe second drug will compensate.

72
Q

Efficacy and selecting drugs.

A

Only drugs known to be somewhat effective when used
alone against a tumor should be selected for use in combination

73
Q

A drug should be selected based on?

A

A drug should be selected based on toxicity that does not overlap with toxicity of other drugs in the combination

74
Q

Optimum scheduling and selecting drugs.

A

Drugs should be used in their optimal dose and schedule, and drug
combinations should be given at consistent intervals. The treatment-
free interval between cycles should be shortest time necessary for
recovery of the bone marrow

75
Q

Mechanism of interaction and selecting drugs.

A

There should be a clear understanding of the biochemical, molecular
and PK mechanisms of drug-drug interaction in each combination.

76
Q

Avoidance of dose changes and selecting drugs.

A

An arbitrary reduction of the dose of an effective drug in order to add more drugs may reduce the effectiveness of the drug and destroy the ability of the combination to cure disease

77
Q

What are the general principles of cancer chemotherapy?

A

❖ In Vet Med, the goal of treatment with a given chemotherapy protocol is
to extend life with an improved quality of life
❖ Therapy is based on an accurate diagnosis and determination of clinical stage
❖ In Vet Med, remission or incomplete tumor control leaving only microscopic disease
is often the most reasonable course of therapy
❖ Palliation of clinical signs, thus improving quality of life without significantly
altering the outcome of disease progression, is a desirable goal for many patients

78
Q

Chemotherapy drugs not only target cancer cells, but they also affect _______ cells
especially of tissues that are rapidly _______, for example the ?. They are therefore commonly associated with side effects like
?
_____ loss is uncommon in veterinary practice. (cats lose _______, poodles and terries may lose _____ on the ____ and ____)

A

normal, multiplying, gonads, hair, skin, and digestive tract

myelosuppression, reduced fertility, loss of hair, mouth ulcers and diarrhea.

Hair, whiskers, hair, face, tail

79
Q

Compared to people who receive chemotherapy, animals experience fewer and less severe side effects. Why?

A

Because we use lower doses of drugs and do not combine as many drugs as in human medicine

80
Q

Chemodrugs have the potential to be?

A

mutagenic, embryotoxic, teratogenic,
carcinogenic, and cytotoxic to normal cells even at low doses

81
Q

Appropriate handling techniques for hazardous drugs are necessary

A
82
Q

Chemotherapy agents can be given via?

A

per oral (PO), intravenous (IV), subcutaneous
(SC), intramuscular (IM), intrathecal (IT). Most of the chemotherapy agents are IV
because of the 100% absorption rate

83
Q
  1. Most of the chemotherapy agents are metabolized and excreted by which organs? 2. Some of the chemotherapy drugs are toxic to which organs?
A
  1. either liver or kidney.
  2. the liver or kidneys. In such cases, toxic levels can build up in these leading to organ dysfunction
84
Q

Chemotherapeutic agents are commonly associated with side effects. Usually, the
side effects of chemotherapy reflect their ?

A

mechanism of action.

85
Q

Development of _______ is a persistent problem during the treatment of local and metastatic cancer

A

chemoresistance

86
Q

What is chemotherapy resistance?

A

Chemotherapy resistance occurs when cancer cells that have been responding to a therapy suddenly begin to grow because any of the following happens:
▪ Cancer cells mutate
▪ Gene (protein) amplification that renders the anticancer drug ineffective
▪ Cancer cells may learn how to repair damaged DNA caused by drugs.
▪ Cancer cells may develop a mechanism that inactivates the drug
▪ Cancer cells may pump the drug out of the cell as a fast as it is going in
using a molecule called P-glycoprotein
P-glycoprotein or MDR protein 1 functions as a biological barrier by extruding
toxins and xenobiotics (drugs) out of cells

87
Q

Cancer cells overexpress ?

A

P-gp
MDR gene/protein alteration/mutation

88
Q

Which dog breeds are at a higher risk of toxicity due to the MDR1 gene mutation?

A

Pharmacology II (27 decks)

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