1
Q
Vincristine and Vinblastine MOA
A
Antimicrotubule agents
Inhibit microtubule assembly (disruption of the mitotic spindle)
2
Q
VinCRISTINE use
A
Lymphoma
Transmissible venereal tumors
3
Q
VinBLASTINE uses
A
Canine mast cell tumors
4
Q
Which chemotherapeutic agents are topoisomerase inhibitors?
A
Epipodophyllotoxins (Etoposide and Teniposide)
But also mitoxantrone (inhibits topoisomerase II)
5
Q
Steroids MOA
A
Induces killing of hematopoietic cancer
cells through interaction with the glucocorticoid receptor and the
induction of apoptosis
6
Q
Platinum (Carboplatin and Cisplatin) MOA
A
Covalent binding to DNA through displacement reactions resulting in bifunctional lesions and interstrand
or intrastrand cross-links.
7
Q
Toxicity with cisplatin
A
Nephrotoxicity
8
Q
Cisplatin/carboplatin use
A
Cisplatin - Canine osteosarcoma (OSA)
Carboplatin - Better tolerated - OSA, other sarcomas and carcinomas
9
Q
Why is carboplatin preferred to cisplatin?
A
Carboplatin is preferred to cisplatin because of the reduced incidence of
nausea/vomiting, the absence of nephrotoxicity, and ease of administration.
10
Q
Hydroxyurea MOA
A
Inhibitor of ribonucleotide reductase - inhibition of DNA synthesis
11
Q
Hydroxyurea clinical use
A
bone marrow disorders such as polycythemia vera and granulocytic
leukemias
12
Q
L-asparginase MOA
A
Hydrolysis of L-asparagine to L-aspartic acid»_space; depletion of L-asparagine»_space; inhibition of protein synthesis»_space; apoptosis
13
Q
L-asparginase use
A
Lymphoproliferative disorders
Relapsed lymphoma
14
Q
Mechlorethamine MOA
A
Alkylating agent (Nitrogen mustard) - DNA cross-linking
15
Q
Mechlorethamine Use
A
Lymphoma in dogs
16
Q
Melphalan MOA
A
Alkylating agent (nitrogen mustard) - direct alkylating activity
17
Q
How is melphalan transported into the cell?
How is transport into the cell blocked?
A
- Transported into tumor cells by amino acid transporters.
2. Blocked by the amino acid leucine.
18
Q
Melphalan use
A
Myeloma
19
Q
Cyclophosphamide MOA
A
Alkylating agent (nitrogen mustard) Bifunctional alkylation and cross-link production.
20
Q
What is the active metabolyte of cyclophosphamide?
A
Phosphoramide mustard
21
Q
What is a major side effect of cyclophosphamide?
A
Hemorrhagic cystitis
22
Q
Cyclophosphamide USE
A
Multiagent protocols for lymphoma in both dogs and cats.
23
Q
Chlorambucil MOA
A
Alkylating agent (nitrogen mustard derivative) Direct bifunctional alkylating ability
24
Q
Chlorambucil clinical use
A
Dogs - control of chronic lymphocytic leukemia (CLL)
Cats - Low-grade GI lymphoma in cats.
25
Lomustine (CCNU) MOA
Nitrosureas-based agent.
DNA alkylation and DNA-DNA and DNAprotein
cross-links
26
Chronic CCNU administration side effect
Hepatic dysfunction
27
Lomustine (CCNU) use
Dogs - multicentric lymphoma, epitheliotropic lymphoma, mast cell tumors, and histiocytic sarcoma.
Cats - Mast cell tumors and lymphoproliferative
disorders.
28
Streptozotocin MOA
DNA alkylation and inhibition of DNA synthesis. Uses GLUT 2 transporter for uptake into cell
29
Streptozotocin use
Streptozotocin is used to manage malignant
| insulinoma.
30
Doxorubicin MOA
Antitumor antibiotic. Multiple effects
1. DNA intercalation and inhibition of RNA and DNA polymerases and topoisomerase II,
2. alkylation of DNA, reactive oxygen generation,
3. perturbation of cellular Ca2+ homeostasis,
4. inhibition of thioredoxin reductase,
5. interaction with plasma membrane components
31
Doxorubicin toxicity in dogs and cats?
Dogs and cats- cumulative dose-related cardiotoxicity
Cats may develop renal tubular damage following repeated dosing
32
Doxorubicin use
Lymphoma, osteosarcoma, (OSA), and most mesenchymal and epithelial neoplasms
33
What is Dexrazoxane (Zinecard)?
Used to reduce cardiac toxicity from doxorubicin use.
Binds to iron in myocardium to prevent free radicals
34
What is mitoxantrone chemically?
Synthetic doxorubicin analog
35
Mitoxantrone MOA
Similar to Doxorubicin but does not cause oxidative. Has anti topoisomerase II.
damage to cells and less likely to generate reactive oxygen species
36
Mitoxantrone use
The clinical indications for mitoxantrone include
| lymphoproliferative disorders and, most recently, transitional cell carcinoma (TCC) of the bladder and urethra
37
Therapeutic index
ratio of the dose of drug required to produce a given probability of toxicity and the dose required to give a defined effect against a tumor
38
○ Induction therapy
more intensified therapy -
| Goal is to ↓ the # of cancer cells & induce a complete remission
39
○ Consolidation therapy
less intensive than induction therapy
- Designed to diminish further the number of cancer cells and to achieve a CR in patients who did not go into CR after induction therapy
40
○ Maintenance therapy
continuation of less intensive chemotherapy protocol to maintain a remission & prevent relapse
41
○ Salvage (rescue) therapy
reinduction chemo for patients who fail one standard protocol
42
○ Stable disease (SD
stable disease at 4 weeks post chemotherapy
43
Cell cycle
○ G0 phase- resting cells
○ G1 phase- RNA and protein synthesis/ cell grows
○ S phase- DNA synthesis
○ G2 phase- 2nd period of RNA and protein synthesis
○ M-phase- mitosis occurs
44
True or False: Cells in resting phase are resistant to chemotherapy
TRUE
45
Progressive disease
Increase in tumor volume of >25% or increase of tumor maximum diameter of >20%; appearance of new lesions
46
Function of the MDR1 (ABCB1) gene
Adenosine triphosphate (ATP)-binding cassette (ABC) transporter family who play a primary role in active efflux of drugs from cells.
47
How is chronic myeloid leukemia diagnosed?
Diagnosis of CML is accomplished by detecting marked
and persistent leukocytosis in the absence of infection, inflammation,
or other neoplasia.
48
What are cats with chronic myeloid leukemia usually positive for?
Feline leukemia virus (FeLV).
49
Characteristics of acute myeloid leukemia
More than 20% blast cells (of whatever lineage is proliferating)
in the blood and bone marrow.
50
Prognosis for acute myeloid leukemias
prognosis for these diseases is grave, and survival is usually measured in weeks
51
Typical treatment of chronic myeloid leukemia?
CML typically is treated with hydroxyurea.
52
Prognosis for chronic myeloid leukemia
Approximately 1 year, although some patients live longer
53
What chemo drugs can you use in MDR1 mutation at-risk breeds?
A non-P-glycoprotein substrate chemotherapy drugs (eg. Alkylators) e.g. cyclophosphamide
54
Does the size of an oral melanoma correlate with prognosis?
Yes, a tumor <2 cm is correlated with better prognosis
55
Tonsillar SCC
more aggressive and metastatic variant of this disease, with a higher rate of metastasis to local lymph nodes (>40%). MST 7-9 months.
56
What breed is at increased risk for AGASACA
Cocker Spaniel
57
What percentage of dogs with AGASACA have hypercalcemia
30%
58
What are the reported MST for AGASACA
Reported survival times range from 6 to 31 months with varying treatments. Best with RT and chemo (mitoxantrone)
59
What is the metastatic rate of transitional cel carcinoma (urinary)
TCC metastasizes to distant sites in approximately 50% of
cases.
Regional lymph nodes, lung, liver, spleen, and, less commonly, kidney, bone, and other organ
60
Is there a sex predilection for transitional cell carcinoma (urinary)?
Females are more affected
61
What is the most common chemotherapy for transitional cell carcinoma (urinary)
mitoxantrone combined with piroxicam
62
What is the MST treating TCC with mitoxantrone and piroxicam
291 days.
63
What is the risk of developing mammary tumors in dogs as compared to their heat cycles and spay?
Spay before first estrus - 0.5%
Spay before second estrus - 8%
Spay after second estrus - 26%
64
What is the malignancy rate of mammary tumors? How many of the malignant tumors will metastasize?
50%/50%
65
Tamoxifen as hormonal therapy for canine mammary tumors
Decrease in tumor burden. Other studies did not have measurable responses. Risk of pyometra/stump pyometra.
66
What chemotherapy agents are used for metastatic mammary tumors?
1. fluorouracil and cyclophosphamide - 24 months (sx and chemo) vs. 6 months (sx alone)
67
Is surgery indicated in inflammatory mammary carcinoma?
Surgery is contraindicated. Wound dehiscence, ventral and limb edema, and disseminated intravascular coagulation all are potential complications of IMC, which is unlikely to be amenable to complete surgical excision.
68
What percentage of feline mammary tumors are malignant?
The majority (80% to 96%) are malignant.
69
What cell type do plasma cell neoplasms arise?
Well-differentiated B lymphocytes that have undergone malignant transformation.
70
What are the most common gammopathies in myeloma (which immunoglobulins)?
IgG and IgA
71
What is Bence Jones/light chain myeloma
Production of pure light chains (κ or λ type)
72
What are the diagnostic criteria for multiple myeloma?
TWO of the following need to be met:
- Monoclonal gammopathy or paraproteinemia
- Radiographic lytic bony lesions
- >5% neoplastic or >10-20% plasma cells in bone marrow
- Light chain (bence jones) proteinuria
- CATS: Plasma cell infiltration of visceral organs
73
Which cell type does osteosarcoma come from?
Osteoblasts
74
What percentage of dogs with osteosarcoma have gross pulmonary metastasis on presentation? What percentage will develop pulmonary metastasis?
Only a small percentage of dogs (~10%) have radiographic
evidence of macroscopic pulmonary metastases at initial
presentation; however, the vast majority (>90%) eventually
develop radiographically evident pulmonary metastatic
disease
75
Where are primary long bone tumors localized usually?
| Where are metastatic long bone tumors localized usually?
Primary bone tumors - Metaphisis
| Metastatic bony tumors - Diaphisis
76
Synchronous disease
Multiple primary tumors (e.g. hemangiosarcoma in heart and spleen)
77
What are some common CBC findings in HSA?
Findings suggestive of microangiopathic process:
Regenerative anemia
Thrombocytopenia
Fragmented RBC (schitocytes)
78
What are the two cell types of the thyroid gland?
1. Thyroid epithelial cells - Synthesis of thyroid hormones
| 2. Parafollicular cells (C cells) - Secrete calcitonin
79
The majority of canine thyroid tumors are malignant (True or False)
True
80
What two types of carcinomas can arise from the thyroid in dogs?
Follicular carcinoma -
| Medullary thyroid carcinoma (C-cell carcinoma)
81
What is the metastatic rate of soft tissue sarcoma according to grade?
Grade I - < 10%
Grade II - 20%
Grade III - 50%
(regional lymph nodes and lung)
82
What are the most common nasal tumors in dogs?
Adenocarcinoma, SCC, fibrosarcoma, chondrosarcoma and osteosarcoma
83
What are the most common nasal tumors in the cat?
1. Lymphoma
2. Carcinoma
3. Sarcoma
84
What is the incidence of primary lung tumors? What is the behaviour? What is the most common primary lung tumor?
Low incidence. The majority of tumors are malignant, and the most frequently reported tumor type is adenocarcinoma in the dog and cat.
85
What are positive prognostic indicators for primary lung tumors?
1. Solitary nodules
2. Peripheral location
3. <5 cm in diameter
86
What are negative prognostic indicators of primary lung tumors?
1. Lymph node involvement
2. More than one nodule
3. Central location
4. >5 cm in diameter
5. High histologic grade
87
Benign vs. malignant thymoma
1. Benign - Well encapsulated and noninvasive
| 2. Malignant - Locally invasive and aggressive
88
What is thymoma's metastatic rate?
Rare
89
What is the signalment for cats with mediastinal lymphoma?
Young (mean 2 y/o) and positive for FeLV
90
Carmustine ( BCNU, BiCNU, Gliadel) metabolism
1. Highly lipid soluble
| 2. Excellent CNS concentrations w/ IV administration
91
Mesna (sodium-2-mercaptoethanesulfonate) - What is it?
Uroprotective agent agent used in humans treated with cyclophosphamide or ifosfamide
92
Ifosfamide metabolims
* Isomer of cyclophosphamide
* Excreted through the urinary tract
* Must be given with mesna (2-mercaptoethane sulfonate) to prevent hemorrhagic cystitis
93
Lomustine toxicity
Dogs may develop potentially fatal hepatotoxicit
94
9 year old dog with Coombs negative hemolytic anemia, hypoalbuminemia, hypochloresteronemia, mildly elevated bilirubin? What is the diagnosis?
Histiocytic disease
95
What chemotherapy drugs cross the blood brain barrier (BBB)
Cytosar (Cytarabine), Lomustine (CCNU), procarbazine, 5-FU
96
What chemo can you give a Collie while waiting MDR gene mutation test results?
Cyclophosphamide - In general any drug produced by a plant or organism will be a P-glycogen substrate and should not be given to MDR mutated dogs
97
What drugs do you NOT want to give an MDR mutated dog?
Do not give vincristine, doxorubicin, mitoxantrone.
| GIVE cyclophosphamide
98
What phase of the cell cycle does Vincristine work on?
M-phase (Microtubule formation)
99
What are paraneoplastic syndromes?
signs, symptoms, and clinical effects associated with underlying neoplasia, but not directly due to physical presence of tumor (humoral, cytokines, immune response)
100
Bleeding diathesis
Coagulation abnormalities due to coating of platelets by paraprotein (hypergammaglobulinemia)
101
Most common cause of hypercalcemia in dogs and cats
Dogs - Cancer
| Cats - Idiopathic or renal
102
What hormones lead to hypercalcemia of malignancy?
PTH-rp - Mimics parathyroid hormone
IL-1B - Osteoclast activating factor
Other: TGF-B, RANKL, Prostaglandin E1/2, extensive bony lysis
103
How does hypercalcemia cause PU/PD?
It decreases response to ADH
104
Paraneoplastic syndrome - Nodular dermatofibrosis
Associated with renal neoplasia (as well as renal cysts)
| - Renal tumors may produce collagen stimulating factors?
105
How does metronomic chemotherapy work?
Inhibits t –regulatory cells (immunomodulation), inhibits angiogenesis
106
Vincristine side effects
GI ileus, neurotoxicity, peripheral neuropathy
107
What is the toxic metabolite for cyclophosphamide?
Acrolein
108
What are some environmental factors for lymphoma?
```
2,4 D (pesticide)
urban environment
paints
solvents
magnetic fields
```
109
What is the most common cutaneous tumor in cats?
Basal cell tumor (slow growing, rarely metastasis, sx often curative)
110
What is the most common oral neoplasia in a dog?
Melanoma
111
What is the behaviour of melanoma in the dog based on the location?
Haired skin - Usually benign
Mucocutaneous, oral, nail bed - Malignant (Metastatic rate 30-75%)
112
What is the behavior of melanoma based on dog breed?
Doberman - Usually benign
Mini Poodles - Usually malignant
113
Characteristics of hemangiopericytoma?
Usually benign, locally invasive
| - Recurrence often after surgical removal
114
Squamous cell carcinoma treatment in cats?
Early aggressive therapy with surgery and RT is best
Chemo not rewarding
115
Squamous cell carcinoma treatment in dogs?
Surgery alone is initial therapy.
| 1 and 2 year survival is 90% and 75%
116
What is the mechanism of mitoxantrone?
Inhibits topoisomerase II and causes DNA intercalation
117
What chemotherapeutic agents are vesicants?
Vinca alkcaloids, doxorubicin, and actinomycin D
118
What are the nitrogen mustard derivative chemotherapeutics?
```
Mechloretamine
Cyclophosphamide
Chlorambucil
Melphalan
Ifosfamide
```
119
Which chemotherapy agents are nitrosureas?
Lomustine (CCNU)
| Streptosozin
120
What are the antitumor antibiotics?
Doxorubicin (Adriamycin)
Mitoxantrone (synthetic derivative of DOX)
Actinomycin D
121
What are the antimetabolite antibiotics?
cytarabine (cytostar)
5-FU
Methotrexate
Gemcitabine (Gemzar)
122
What are the antimicrotubule agents?
```
Taxanes (Paclitaxel and Docetaxel)
Vinca alkaloids (Vincristine, vinblastine)
```
123
Birt-Hogg-Dube gene
Associated with renal cystadenocarcinoma and nodular dematofibrosis (RCND). German shepherds predisposed.
124
Bowen's carcinoma
Squamous cell carcinoma in situ at multiple sites - primarily in cats
125
What is actinic keratosis?
Squamous cell carcinoma in situ due to UV exposure
126
What is the most common tumor of the digit?
Squamous cell carcinoma (both dogs and cats)
Dogs: SCC most common, followed by melanoma
Cats: SCC, fibrosarcoma, adenosarcoma
127
What IHC marker predicts malignancy in melanoma?
Ki67 IHC predicts potential malignant behavior
128
What do mast cell tumor granules stain with?
Giemsa
| Toulidine Blue
129
What is Darier's sign in mast cell tumors?
Mechanical manipulation of a MCT that causes degranulation and subsequent erythema and wheal formation in surrounding tissues
130
What are paraneoplastic syndromes of leiomyomas and leiomyosarcomas?
HYPOGLICEMIA, nephrogenic DI, secondary erythrocytosis
131
How often is malignant melanoma amelanotic?
1/3 of the time
132
Most common pituitary tumors in dogs and cats
Dogs - Corticotrophic adenoma - causes ADH (release of ACTH)
Cats - GH-secreting somatotroph adenoma (acromegaly, diabetes)
133
What is Conn's syndrome?
Primary hyperaldosteronism from an adrenal tumor
134
Pheochromocytomas are tumors of what cells?
Chromaffin cells in the adrenal medulla
135
What is the most common primary brain tumor?
Meningioma, followed by glioma
136
What is the most common tumor that mets to the brain in the dog and cat?
Dog - Hemangiosarcoma
Cat - Lymphoma
137
What is the double 2/3 rule for hemangiosarcoma?
2/3 dogs with splenic masses have malignant tumors, 2/3 of those have HSA
138
What does the Birt-Hogg-Dube gene encode?
Folliculin - tumor suppressor gene
139
Most common digit tumor in both dogs and cats?
Squamous cell carcinoma
140
What IHC predicts malignancy in melanoma?
Ki67
141
What stain is needed for mast cell tumors that do not stain with DiffQuik?
Giemsa
142
In what dog breeds is mast cell tumor more benign?
Boxer
Pugs
Bulldog
143
What are the surgical margins for mast cell tumor?
3 cm around, 1 fascial plane deep.
Low grade 1-2 cm may suffice
144
Are wide margins necessary for feline cutaneous mast cell tumor?
No
145
What parasite has been associated with esophageal soft tissue sarcoma?
Spirocerca lupi
146
What are paraneoplastic of leiomyosarcomas and leiomyomas?
HYPOGLYCEMIA
Nephrogenic DI
Erythrocytosis
147
What intestinal tumor is associated with C-kit mutation (CD117)?
GIST
148
What STS has a higher rate of lymph node metastasis as compared to other STS?
Synovial cell sarcoma
149
What is the 3-2-1 rule for suspected injection site sarcoma in cats?
Treat if:
- Mass still present >3 months after vaccine
- Larger than 2 cm
- Or increasing in size >1 month after vaccine
150
What is a feature of oral fibrosarcoma?
Histologically low grade, but biologically high grade
151
What is the more common hepatobiliary tumor in cats?
Bile duct carcinoma
152
What is a carcinoid?
Tumors that arise from the diffuse endocrine system in the GI rather than the epithelium
Enterochromaffin cells - Secrete serotonin, somatostatin, etc
153
What additional therapy is recommended with perianal adenoma?
Castration
154
How do you differentiate osteosarcoma (histo) from other connective tissue tumors?
ALP stain
155
What is codman's triangle?
As tumor invades the cortex and the periosteum is elevated, new bone is laid down on the cortex at the periphery in a triangle-fashion
156
What is multiple cartilaginous exostosis in cats associated with?
FeLV
157
What is the treatment and prognosis in cats with multiple cartilaginous exostosis?
Amputation - Guarded prognosis as local recurrences are common and no known effective treatment
158
What is a medical therapy for pheochromocytoma?
Phenoxybenzamine
159
What is the most common metastatic brain tumor in dogs? Cats?
Dogs - hemangiosarcoma
| Cats - Lymphoma
160
Brain meningiomas are extra-axial. What does this mean?
attach outward and move in
161
Surgically, how do feline and canine brain meningiomas differ?
Cats - Generally peel away easily
Dogs - Harder to predict
162
What are common locations for peripheral nerve sheath tumors?
CN - V
| Spinal - Brachial plexus
163
What CD markers are expressed by B cells?
CD79a
CD20
CD21
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