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Small Animal Medicine II > Cancer Treatments > Flashcards

Cancer Treatments Flashcards

(90 cards)

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1
Q

What to considerations do you need to consider prior to treatment?

A

Histologic type and biologic behavior
Grade of tumor
Stage of disease

Morbidity/mortality of therapy (toxicity)
Survival for this tumor type with the treatment regime
Cost of therapy

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2
Q

Surgery

Benifit

A

Only way to actually remove cancer; cures more patients than any other modality

How to get appropriate staging

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3
Q

Surgery

Common mistake

A

Not taking large enough margins on first surgery (need wide margins; 3 cm of normal tissue)

Not submitting all tissues removed and marking margins

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4
Q

Surgery

What happens if tumor not completely excised?

A

Tumor will recur

Alters vascularity, immune system, and tissue planes => recurring tumors are more aggressive, subsequent surgeries more difficult

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5
Q

Surgery

Limitations

A

Localized tumor, not useful if tumor has or will metastasize (grade and staging important); usually still have to do chemo

Some areas there is only so much you can remove

Cats are not as amendable to removal

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6
Q

Radiation Therapy

A

Deposition of energy on or near DNA (breakage of DNA)

Cells die when they try to divide

Kills a constant proportion of cells

Damages normal and cancer cells

Iodine 131 is the only direct radiation; will kill only cancer cells

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7
Q

Direct DNA Damage

A

Radiation therapy

Direct ionization
Chemical bonds broken through DNA; lethal damage and double stranded break

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8
Q

Indirect DNA Damage

A

Radiation therapy

Bonds broken through the ionization of water and the formation of damaging reactive radicals

Oxygen required to perpetuate damage

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9
Q

Radiation therapy

Limitations

A

Local disease only (tumor size)
Surrounding normal tissue must tolerate radiation
Radiation sensitive tumor type (oxygen must be able to get to the location)
Anesthesia requirement because patient needs to be completely still

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10
Q

What are the four R’s of Radiation Therapy

A

Repair
Repopulation
Re-oxygenation
Redistribution

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11
Q

Radiation Therapy

Repair

A

Save normal cells

Damaging cells but cells with normal DNA repair will fix themselves (6 hours)
Cancer cells do not have correct repair mechanisms; DNA is wonky anyway

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12
Q

Radiation Therapy

Repopulation

A

Number of clonogenic tumor cells

Rely on epithelial cells; wound healing mechanisms

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13
Q

Radiation Therapy

Reoxygenation

A

Kills cancer cells

Oxic and hypoxic

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14
Q

Radiation Therapy

Redistribution

A

Given time post one dose of radiation all remaining cells move towards mitosis, and towards increased sensitivity

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15
Q

Radiation Therapy

Goal

A

Time period allowing reoxygen and redistribution in tumor, repopulation and repair in normal cells

Large total dose (tumor control)

Small fraction (less late effects)

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16
Q

Radiation Therapy

What are late effects?

A

Necrosis of tissues:
Bone, brain, etc.
Skin fibrosis

Alopecia, hyperpigmentation, cataracts

May not live long enough to get the late side effects

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17
Q

Radiation Therapy

Size of Tumor

A

Larger tumor is difficult to treat mechanistically
Radiation kills only a portion each time
Larger size, more hypoxia

Gompertizian growth; exponential growth of cancer cells (tumor not palpable until it is 1 gram; 10^10 cells!)

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18
Q

Radiation Therapy

Acute effects

A 
Fast dividing cells:
Hair loss
Moist dermatitis
Mucositis (conjunctiva, oral cavity, nasal passages)
Intestine or bladder inflammation
Nervous tissue inflammation/edema
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19
Q

Radiation Therapy

Skin

A

No longer than 2-3 weeks
Hair loss, mild erythema of skin (no treatment needed)

Custing oozing skin; aloe vera, aquaphor, NSAIDs, pain medication

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20
Q

Radiation Therapy

Conjunctivitis

A

1-2 weeks

Antibacterial opthalmic ointment, NO steroids

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21
Q

Stereotactic Radiation Therapy

A

Few very large doses of radiation versus many small ones

May kill cells not rapidly dividing better than traditional

May damage blood supply more than tumor

Must be done close to tumor

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22
Q

Chemotherapy

Mechanism

A

Act on rapidly dividing cell populations by interfering with DNA synthesis or cell division

Highly non-specific; exploits a macro difference in cells

Only therapy for metastatic disease

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23
Q

Chemotherapy

Alkylating Agents

A

Chlorambucil
Cyclophosphamide
Lomustine
Melphalan

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24
Q

Chemotherapy

Antimetabolites

A

Cystosine Arabinoside
Methotrexate
Elspar
Azothioprine

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25
Chemotherapy | Antitumor Antibiotics
Bleomycin Anthracyclines Doxorubicin
26
Chemotherapy | Spindle Cell Poisons
Vinblastine Vincristine Taxols
27
Chemotherapy | Platinum drugs
Carboplatin | Cisplatin
28
Chemotherapy | Limitations
Resistance/Multiple drug resistance (multiplies fast) Drug may not be able to make it to tumor site ``` Side effects to normal tissues: bone marrow alopecia allergic reactions GI ```
29
Chemotherapy | Rx: Kidney side effects
Cisplatin Doxorubicin (cat) Lomustine (chronic)
30
Chemotherapy | Rx: Heart side effects
Doxorubicin
31
Chemotherapy | Rx: Bladder side effects
Cyclophosphamide
32
Chemotherapy | Rx: Pancreas side effects
Elspar | Doxorubicin
33
Chemotherapy | Rx: Nervous system side effects
``` Vincristine 5 FU (cats!) ```
34
Chemotherapy | Rx: Hepatic side effects
Lomustine
35
Chemotherapy | Rx: Lung side effects
Cisplatin (cat) Bleomycin Lomustine
36
Chemotherapy Protocols | Multiple Drugs
Single drugs are unlikely to cure bulky disease Multiple drugs may help fight development of resistance Toxicity may be less with low doses of multiple drugs vs. large doses of single drugs
37
Chemotherapy Protocols | Single Agent
Common because not much is known about efficacy of individual drugs
38
What neoplasias do soly using chemotherapy work for?
Lymphoma Germ cell tumors Transmissible venereal tumors
39
Neoplasia treatment recommendation
Surgery and Chemotherapy
40
Chemotherapy | Dose
BSA (m^2) Too much can kill the patient
41
Chemotherapy | Monitoring
Timing CBC Chem Careful venipuncture
42
Chemotherapy | Quick IV
Lateral saphenous or cephalic (dogs) Medial saphenous (cats) Butterfly or indwelling catheter
43
Chemotherapy | Slow administration
Infusion to decrease cardiac toxicity Severe tissue reactions if extravasated (Doxorubicin) Must clearly see vein Flush with saline Constant monitoring; someone sits with patient
44
Cyrotherapy
Only successful with tumor is small and superficial SCC sometimes
45
Evaluation of Treatment Results
Survival: length of time post diagnosis an animal will live (average) Time to recurrence or relapse; end of treatment to tumor reappearance Time to tumor progression/recurrence Prognostic indicator
46
What are "macro" differences between cancer and normal cells?
Proliferative rates DNA synthesis rates Ineffecient repair of damage
47
Signal Transduction Therapy | What is it?
Aberrant signal transduction elements present in most cancers Mutated signal proteins often oncogenic Consitutive activation of signaling elements (is cell itself secreting the factor to keep it alive?)
48
Signal Transduction | Cancer Physiology
Expression of growth receptors and/or mutated signal transduction elements related to: Increase in potential for proliferation, invasion, metastasis Increased angiogenesis Cancer can support self Shortened survival of patients Poor response to chemo Poor prognosis
49
Signal Transduction Therapy | Example
Receptor tyrosine kinases (RTKs) Main mediators of the signaling network that transmit extracellular signals to the cell Controls cellular differentiation and proliferation
50
RTKs | Mechanism
Signal Transduction: Receptor tyrosine kinases RTK signaling -> dysregulated cell growth -> cancer Overexpression of RTK proteins Functional alterations caused by mutations in corresponding genes (gain of function) Abnormal stimulation by autocrine growth factor loops (increased stimulation) Once started are on for life until effect is gone
51
RTKs | Primary targets
EGFR-HER-2 c-Kit VEGFR
52
What is EGFR-HER-2
RTK | Epidermal growth factor receptor
53
What is c-Kit
RTK | Proto-oncogene coding for RTK
54
What is VEGFR
RTK Vascular endothelial growth factor receptor Angiogenesis
55
c-Kit | Mutations
9-33% of MCTs have c-Kit mutations | Higher tumor grades associated with more frequent c-Kit mutations
56
Toceranib What is it? Response to Grade II
RTK Inhibitor: Palladia Response to grade II: 42.8%
57
What neoplasias have RTKs been used in?
``` Thyroid carcinoma Anal gland adenocarcinomas Hemangiosarcoma Soft tissue sarcomas Lymphoma Histiocytic sarcoma Vaccine associated sarcomas ```
58
Angiogenesis | Background
Tumor growth is dependent on vascular growth: neovascularization required for growth Delivery of nutrients, growth factors, hormones, oxygen Removal of wastes and toxins Immune surveliance Is different than normal vasculature
59
Targeting tumor blood vessels | How?
Vascular disrupting agents (VDAs): Given only intermittently Designed to induce rapid and selective vascular shutdown in tumors Suppression of endothelial cell growth and recruitment from bone marrow (only good in small tumors)
60
Targeting tumor blood vessels | What treatment modality cannot be used then?
Radiation because it needs the vascular oxygen supply to cause damage and to help normal cells develop
61
Targeting tumor blood vessels | Biologics
Antibodies or peptides that deliver toxins and procoagulant and pro-apoptotic effectors to tumor endothelium VEGF = target Avastin in humans Not available for vet med
62
Targeting tumor blood vessels | Two categories
Biologics Small molecules
63
Targeting tumor blood vessels | Small molecules
Agents that exploit known differences between tumor and normal endothelium to induce severe vascular dysfunction (blocking receptors) Examples: Thalidomide (not allowed; very teratogenic) Toceranib (c-Kit) - direct inhibitor of VEGF
64
What is metronomic chemotherapy?
Low daily dosing of traditional drugs Stop endothelial cells from multiplying in, and homing to neoplastic tissues Most effective in prevention of metastasis or tumor regrowth Not effective for large tumors
65
``` Metronomic chemotherapy Drugs used (4) ```
Chlorambucil Cyclophosphamide Lomustine Satraplatin
66
Chlorambucil | Uses
TCC MCT Thyroid
67
Cyclophosphamide | Uses
Soft tissue sarcomas MUST let animal outside often; will have to pee frequently or will cause bladder damage
68
Apoptosis | Two Pathways
Intrinsic (mitochondrial) Extrinsic (receptors)
69
Apoptosis | Intrinsic Pathway
Affected by conventional therapies (Radiation and other traditional Chemos) Mutations commonly occur rendering tumors resistant to conventional therapies
70
Apoptosis | Extrinsic Pathway
Novel therapies targeting here may circumvent resistance Caution; could cause all cells to apoptose
71
Immune Tolerance Tumors Target Idea
Tumors avoid immune system via variety of mechanisms; main one being recognized as "self" Immune therapy; attempt to get immune system to recognize a tumor as something to destroy
72
Immune Therapy | 3 Kinds
Active Nonspecific - Immune Stimulation Active Specific - Tumor Vaccines Passive - Antibody Administration
73
Immune Therapy | Active Nonspecific
Goal: immune stimulation Intact bacteria (potent) of cell components Chemical agents (COX-2 inhibitors, Levamisole) Vitamins/minerals Growth factors (activate lymphatics) IL-2, IFN-alpha
74
Immune Therapy | Active Specific
Vaccines Genetically engineered antigen source designed to stimulate an immune response against established tumor Increase immune reactivity to tumor antigens: Cytokines Molecules Adjuvants
75
Immune Therapy | Tumor Vaccine
Activate T-cells (increase MHC on cell surface) Activate antigen presenting cells Get the destruction stimulated!
76
Melanoma Vaccine
Immune Therapy-Tumor Vaccine Murine (mouse) Tyrosinase DNA: source of melanoma differentiated antigen Licensed only for dogs with oral melanomas
77
Immune Therapy Passive Immunotherapy Examples (2)
Monoclonal antibodies specific for tumor Target specific antibodies: VEGF (ostesarcoma; HER-2) RTK (Herceptin; breast cancer in humans) More research needed
78
Immune Therapy | Target T-regulatory Cells
Destroy immunosuppressive environment around tumor May use conventional drugs (metronomic chemo, Cimetidine) Cancer has made the immune system their b!tch and we are trying to stop that
79
COX-2 Inhibitors Piroxicam Use
Osteosarcoma | Seen to shrink tumors
80
Cyclooxygenase | What is it?
Key enzyme in conversion of arachidonic acid to prostanoids COX-1 and COX-2
81
COX-2 | Where do you see this?
``` Pro-inflammatory Growth factors Mitogenic substances Oncogenes Hypoxia ```
82
COX-2 and Cancer Specific target Drug that targets this
Tumor promoting activities-PGE2 ``` PGE2 Function: Conversion of pro-carcinogens to carcinogens Stimulation of tumor cell growth Prevention of apoptotic cell death Promotion of angiogenesis Immune suppression ``` Note: Galliprant targets PGE2!
83
COX-2 Expression in what tumors
``` TCC Renal cell carcinoma Oral SCC GI tumors Mammary tumors Nasal tumors Ovarian Carcinomas Prostatic Carcinomas Canine intracranial meningiomas Canine melanoma (ocular and oral) ```
84
Piroxicam Alone What does it have? What tumors?
COX-1 and COX-2 SCC oral cavity dogs and cats Nasal tumors Inflammatory mammary carcinoma (better than chemotherapy)
85
Piroxicam plus Chemotherapy | What tumors?
Cisplatin for Oral SCC Carboplatin for Oral non-tonsilar SCC Metronomic cyclophosphamide for soft tissue sarcomas
86
NSAIDs and Cancer Prevention?
71% tumor reduction in dogs receiving long term NSAID therapy Carcinomas: 91% reduced MCT: 94% reduced Note: the higher the MCT grade the more COX-2 present
87
COX-2 in Cats | Drug Examples
Meloxicam or Piroxicam Note meloxicam could cause kidney issues so monitor this
88
COX-2 in Cats | Tumor Examples
TCC Oral/Cutaneous SCC Mammary carcinoma GI carcinomas
89
COX-2 in Dogs | Drug Examples
Deracoxib | Fibrocoxib (Previcox)
90
NSAID overall response to Cancer
Not curative but can help suppress growth

Small Animal Medicine II (17 decks)

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