Pharmacology of anti-cancer drugs Flashcards
(211 cards)
1
Q
What does cancer treatment depend on?
A
- Type of cancer
- Grade
- Stage
- Known biological behavior
2
Q
Grade
A
- Pathological term
- Degree of differentiation based on histopathology
- Mitotic index - # of mitoses seen in 10 HPF (higher = higher likelihood of metastasis)
- Other marks are often specific for tumor type
3
Q
AgNor scores
A
- Mast cell tumor marker
- Argyrophilic (silver staining) nucleolar organizing regions within individual nuclei
- Higher score = higher likelihood of metastasis
4
Q
Tumor staging
A
- Are metastases present?
- Looking at the patient
- Later stage disease means more global therapy
- What is overall tumor load?
5
Q
Osteosarcoma behavior
A
- Thoracic radiographs at time of dx
- Most have no visible pulmonary metastasis, but 90% of canine osteosarcoma patients will die within 1 year of diagnosis (pulmonary metastases)
- Must consider treating systemic disease
6
Q
Other factors considering for cancer tx
A
- Location (e.g. if in CNS)
- Oncogenes
- Receptors
- MDR1 status
7
Q
What are the three primary methods of treatment for cancer?
A
- Surgery (super important)
- Radiation therapy
- Systemic disease (some localized tumors): chemotherapy
8
Q
Treatment of choice for small, localized tumors
A
- Surgery
- Any tumor that is low grade, low stage, and cleanly removed
- Suggests that you don’t need chemotherapy
9
Q
Idea of selective toxicity of chemotherapy
A
- Toxic to cancer cells but safe for normal cells
10
Q
How do cancer treatments accomplish selective toxicity?
A
- Select for characteristics of cancer cells not shared by normal cells
- Rapid proliferation
- Angiogenesis
- Ability to manipulate immune cells and microenvironment
11
Q
Rapid proliferation of cancer cells
A
- MOST cancer cells
- If chemo is going to be successful, often need to be rapidly proliferating
- Enzymes, substrates related to: DNA synthesis, DNA structure, and DNA function
12
Q
Angiogenesis
A
- Tumors will need to develop their own blood supply in order to survive
13
Q
What are the 5 stages of the cell cycle?
A
- M
- G1
- G0
- S
- G2
14
Q
How long does mitosis last? What relative proportion of cell cycle (generally) does it take up?
A
- 1-7 hours
- Enough to pull the DNA apart
- Small % of cell cycle
15
Q
What drug class works during mitosis?
A
- Vinca alkaloids
- I guess radiation works well here too
16
Q
How long does G1 last?
A
- 7-170 hours
17
Q
What is occurring during G1?
A
- RNA transcription (mRNA produced)
- Protein synthesis
- Proteins required for DNA replication are produced during this phase
18
Q
What drug class works during G1?
A
- Not many
19
Q
What happens during S-phase?
A
- DNA synthesis in preparation for chromosomal duplication (8-30 hours)
20
Q
What drug class works during S phase?
A
- Antimetabolites
21
Q
How long does G2 last?
A
- 1-4 hours
22
Q
What happens during G2?
A
- Pause prior to mitosis
- Likely to be organization of proteins and cellular machinery required for mitosis
23
Q
How long does G0 last?
A
- Can be for years
24
Q
What happens during G0?
A
- Cells that aren’t actively cycling (replicating)
- Neurons, muscle cells do not re-enter cell cycle
- Hepatocytes normally do not re-enter cell cycle after maturity, but can readily do so
25
What dictates in which phase of the cell cycle a drug acts?
- Mechanism of action
26
What is consequence of a drug not being cell cycle specific?
- might kill non-replicating cells as easily as replicating cells
- Not many anti-cancer drugs are not this category
27
Cell cycle specific vs phase specific drugs in terms of dosing frequency
- Phase specific you might have to give more often
| - Most drugs are cell -cycle specific
28
What is fractional kill?
- Chemotherapy kills a constant FRACTION of cells, not a constant NUMBER of cells
- Depending on tumor type and agent involved this can be 10% to 99.9%
- Nothing will give you 100%
29
What number of tumor cells is incompatible with human life?
- 1 kg or 10^12 cells
| - Not sure
30
Tumor growth doubling time?
- how long it takes to double population
| - Only takes one growth cycle to double
31
How many doubling times has a 1 g tumor undergone if it started from 1 cell?
- 30 doubling times
32
How long does it take to get from 10 g (diagnosis) to 1 kg (incompatible with life)?
- Only 10 more doubling times
| - Short doubling time is 1 month
33
How small are the smallest tumors usually that we can detect?
- 1 g
| - 1 billion (10^9 cells)
34
Fractional cell kill charts
- look at them in the notes
35
What limits chemotherapy dose and interval?
- Host toxicity
36
What can lead to chemotherapy failure?
- Toxicity to host
| - Development of a drug-resistant cell population****
37
What is a common interval used for chemotherapy drugs?
- Often three week intervals at best
| - Allows repopulation of tumor cells
38
What are chemotherapeutic resistance mechanisms?
1. Altered target
2. Inactivation of drug
3. Failure to reach target
4. Failure to undergo apoptosis (unique to cancer cells)
39
DNA topoisomerase enzymes
- essential for DNA replication (mammalian form of DNA gyrase)
- Mutations in enzyme occur in tumor cells to cause resistance
40
Which mechanism of chemotherapeutic resistance can happen in DNA topoisomerase enzymes to doxorubicin?
- Alteration of the target
41
Which drug targets DNA topoisomerase enzymes?
- Doxorubicin
42
Inactivation of drug definition
- Detoxifying mechanisms in normal cells also present in neoplastic cells that can be overexpressed
43
Example of a drug that is inactivated by some tumors
- Alkylating agents like cyclophosphamide
- Glutathione-S-transferase system "detoxifies" alkylating agent
- Tumor cells that over-express glutathione-S-Transferase can be resistant
44
Which of the chemotherapeutic resistance mechanisms is most important?
- FAILURE TO REACH TARGET
45
What protein is often implicated in the failure of chemotherapy drugs to reach their target?
- Transport pumps like P-glycoprotein
- They will pump chemotherapy drugs out of the cell or our of the cell nucleus
- #1 cause of MDR
- Tumors can already have P-glycoprotein (e.g. BBB, hepatocytes, pulmonary parenchyma, or bladders) or develop it
46
What drugs that we learned about can fail to reach the target as a consequence P-glycoprotein overexpression?
- Doxorubicin
- Vincristine
- Vinblastine
- Taxanes
47
What is the ultimate method by which each chemotherapeutic agent has been shown to kill cells?
- Inducing apoptosis
48
What are the two factors that contribute to apoptosis?
- Pro-apoptotic genes
| - Anti-apoptotic genes
49
How can tumors overcome apoptosis?
- Many tumors overexpress bcl-2 (anti-apoptotic)
| - Also tumors with mutations in tumor suppressor gene p53 can be resistant to apoptosis
50
What is a complete response to chemotherapy? (Classic)
- Resolution of clinically apparent disease (e.g. palpable masses, radiographic disease, leukemic cells, paraneoplastic syndromes)
- For at least one month
51
Partial response to chemotherapy (Classic)
- Reduction of measurable tumor dimensions by at least 50% for 1 month duration
52
Stable response to chemotherapy (Classic)
- No change
| - <50% reduction in tumor dimensions
53
Progressive disease response to chemo (Classic)
- Growth of lesion or appearance of new lesions
54
Resist criteria complete response
- Tumor not detectable
55
Resist criteria partial response
- Greater than 30% decrease in longest dimension
56
Resist criteria stable
- Less than 30% decrease or less than 20% of tumor growth
57
Resist criteria progressive
- greater than 20% of increase in longest dimension observed
58
Clinical trials overview
- NIH and pharm companies screen hundreds to thousands of synthetic and natural compounds against a panel of tumor cell lines
- Compounds that show efficacy are tested for toxicity in rodents
- Those compounds with efficacy and relative safety in rodents may proceed to Phase I clinical trials (only a fraction make it past this hurdle)
59
Phase I clinical trial (not super important)
- Recruit patients with advanced tumors for which no effective treatment is available
- Goal to determine max tolerated dose
- Dose escalation
- Progress to Phase II if ANY efficacy emonstrated against any tumors
60
Phase II clinical trial
- Goal to determine which tumor types the drug seems to have efficacy for
- Recruit patients with advanced tumors of various types
- More info gained about dosing
- If activity is demonstrated against a particular tumor type, drug progresses to Phase III
61
Phase III clinical trial
- Goal to determine if drug candidate and other drugs = improvement over current gold standard
62
What is the general standard for vet med drugs?
- less rigorously screened and really only need to be "safe"
- To receive a conditional approval, a drug company must prove, among other things, that the animal drug is safe and has a "reasonable expectation of effectiveness"
63
What does Body surface area (AKA meter squared) correlate better with?
- Cardiac output
- Glomerular filtration rate
- Basal metabolic rate
64
What does BSA not seem to correlate better with?
- Bone marrow stem cell turnover
65
BSA of an 8.5 lbs dog
0.25 M2
66
BSA of a 24.5 lb dog
0.5 M2
67
BSA of a 70 lb dog
1 M2
68
BSA of a 128 lb dog
1.5 M2
69
How to calculate BSA in M^2?
- [Km x (W^2/3)]/(10^4)
```
w= weight in grams
Km = species factor
```
70
What correlates better with myelosuppression: BSA or body weight?
- Body weight
- Dogs <10 kg more likely to develop myelosuppression if dosed based on BSA as compared to body weight
- They always say 30 mg/(M^2) unless less than 10 kg
71
What are the three most common chemotherapy toxicities?
- BAG
- Bone marrow
- Alopecia, anaphylaxis, or allergy
- GI
72
Infertility and chemo drugs
- It will impact
| - need to collect semen before starting chemotherapy
73
Why do dogs not typically get alopecia on chemo?
- Mostly for rapidly dividing cells (in people, hair cells)
| - Dogs have fur not hair
74
Why do we see bone marrow suppression with chemo?
Rapidly dividing cells
75
Which order are cell lines affected by chemotherapy first?
1. Neutrophils (do a CBC post 1 week getting chemotherapy drug)
2. Platelets
3. RBCs (take 120 days; if they drop sooner, worry that we made the cells fragile or have a GI bleed)
76
Alopecia with chemo drugs in dogs
- Hair follicles are rapidly dividing
- Dogs and cats don't have constantly growing hair, but some breeds are more affected (e.g. poodles, old English sheepdogs)
- Cats may lose whiskers and can become really soft due to losing their guard hairs
77
Signs of GI toxicity with chemo drugs
- Anorexia, Nausea, vomiting, diarrhea
78
Relative frequency of GI toxicity in veterinary patients taking chemo drugs
- Less common in veterinary patients than human
| - Not sure the cause (dose? Less cerebral input? Metabolic differences?)
79
Cisplatin mode of nausea
- Directly tells the brain to vomit
80
Cisplatin how to prevent nausea?
- Premedicate to prevent nausea
81
Which chemo drugs are most associated with GI toxicity?
- Cisplatin
- Lomustine
- Doxorubicin
82
Lomustine mode of nausea
- Directly tells the brain to vomit
83
Lomustine how to prevent nausea?
- Give at bedtime to allow sleeping through nausea
- Vomiting more in dogs than in cats
- With cats look more for anorexia
84
Doxorubicin mode of nausea
- Colitis
85
How to mediate nausea with doxorubicin?
- Fiber or bland diet
86
Infertility and chemo drugs - which sex?
- BOTH males and females
87
Can chemo drugs cause congenital malformations?
- ABSOLUTELY
88
What do you consider when determining a maximum tolerated dose?
- Owner (e.g. owner wants no vomiting or diarrhea)
| - Patient (for an MDR1 dog you won't give the same maximum tolerated dose)
89
Maximum tolerated dose in a patient undergoing palliative care?
- tolerate fewer side effects
| - Want to cause no harm whatsoever
90
Maximum tolerated dose in a patient undergoing curative therapy?
- May tolerate greater side effects
91
Three main guidelines of chemotherapy
1. ) DO NOT USE EMPIRICALLY
2. ) Agent must have efficacy for tumor
3. ) Monitor with objective criteria
92
Three safety considerations for people handling chemotherapeutic agents (as well as the patients)?
- Carcinogenic
- Mutagenic
- Teratogenic
- Remember that animal waste may contain the active drug
93
Safety considerations for preparing chemo drugs
- Low traffic area
- Safety hood
- Gloves
- Closed systems/chemo pins
- Always wear gloves!!!!
- Often need to be double bootied, double gloved, full face shield, and gowned
94
Pill handling chemo drugs
- DO NOT CRUSH UP PILLS
95
MOA of alkylating agents
- Interfere with DNA replication
- Several mechanisms
1. ) Alkylates DNA bases. When repair enzymes attempt to repair, they don't recognize abnormal bases, leading to fragmentation of DNA.
2. ) Cross bridges form between alkylated bases --> prevention of DNA separation for synthesis or transcription.
3. ) Mispairing: instead of adenine-thymine and cytosine-guanine, alkylated guanines pair with thymidine lead to mutations. (THIS can lead to toxicity in the patient or owners).
96
Route of alkylating agents
- Oral often
| - Very bioavailable
97
Examples of alkylating agents
- Cyclophosphamide
- Lomustine
- Chlorambucil
- Melphalan
98
Nadir for Cyclophosphamide BAG effects
- 7-14 days
| - This is the white cell nadir
99
Side effects of cyclophosphamide
- BAG (bone marrow suppression especially
| - Sterile hemorrhagic cystitis
100
Sterile hemorrhagic cystitis associated with cyclophosphamide
- Metabolite (acrolein) accumulates in urine
- Irreversible
- Prevent by increasing water intake and encouraging frequent voiding (can give prednisone or diuretics)
- They need to go out every 4 hours 3 times a day
- Doesn't matter if low or high dose
101
Lomustine toxicity
- BAG (bone marrow suppression definitely the big one)
- Chronic neutropenia or thrombocytopenia
- Hepatic, renal, and lung toxicity long-term
102
When is the nadir for neutropenia or thrombocytopenia with lomustine?
- 1-3 weeks
| - Should continue to monitor the white count
103
How to avoid GI toxicity with lomustine?
- Give at night
104
How to prevent or mitigate hepatic, renal, and lung toxicity long-term?
- Monitor chemistries serially
| - Dr. Sellon will put on protectants if giving this drug; Dr. Fidel monitors
105
Chlorambucil toxicity
- BAG (less of an issue)
| - This is often what they switch to if cyclophosphamide doesn't work
106
Primary alkylating agent used for lymphoma protocols?
- Cyclophosphamide - 1°
- Lomustine is a rescue; can penetrate CNS
- Chlorambucil for low grade lymphomas
107
Which drug typically is used for low grade lymphomas?
- Chlorambucil
108
Which alkylating agent is used for mast cell tumors and histiocytic sarcomas?
- Lomustine
109
Alkylating agents other use
- Component of protocols for a variety of other tumors, e.g. HSA
110
General dosage range with alkylating agents
- Metronomic therapy, given at low constant dose to suppress angiogenesis
- Sometimes shrinking but more keeping them stable in size
111
General MOA of mitotic inhibitors
- Bind microtubules, thereby interfering with cell division
112
Examples of Mitotic inhibitors
- Vinca alkaloids (Vincristine, Vinblastine)
| - Taxanes (Paclitaxel)
113
Toxicity of Vinca alkaloids (mitotic inhibitors)
- BAG
- Vesicant (one-stick protocol; not so terrible)
- Neurotoxicity
114
Which vinca alkaloid is more bone marrow suppressive?
- Vinblastine more than vincristine (potentially)
115
Neurotoxicity of vinca alkaloids (mitotic inhibitors)
- This is more FYI
- NT gets from cell body down to where it needs to get released by traveling via tubules
- If you interrupt those tubules you don't get the neurotransmitter
- Peripheral neuropathy
116
Paclitaxel
- mitotic inhibitor that is not in use anymore
117
Paclitaxel toxicity
- BAG
- Causes a pretty bad neutropenia
- Vomiting and anorexia are severe
118
What tumors is vincristine used to treat?
- Lymphoma protocol component
| - Transmissible venereal tumor
119
What tumors is vinblastine used to treat?
- Canine mast cell tumor
| - Lymphoma
120
WHat tumors is paclitaxel used to treat (or used to be used to treat)?
- Squamous cell carcinoma
- Mammary tumors
- Don't use vincristine or vinblastine for these
121
Route of mitosis inhibitors
- Injectable only
122
Mechanism of cancer "antibiotics"
- Many proposed
1. INHIBITION OF TOPOISOMERASE is the big one***
2. Intercalation into DNA
3. Interfere with DNA as well as RNA synthesis
123
Antitumor antibiotics specificity (e.g. cycling vs phase specific)
- Have to be cycling but not in a specific phase
124
Role of topoisomerase II enzyme complex
- Unwinds DNA for transcription
125
Specific effect of doxorubicin on topoisomerase II
- Stabilizes the DNA in the "broken" or wound DNA configuration
126
Examples of anti-tumor "antibiotics"
- Doxorubicin (Ariamycin)
| - Mitoxantrone
127
Toxicity of Antitumor antibiotics (doxorubicin and mitoxantrone)
- BAG (wipe out WBCs)
- Cumulative cardiac toxicity (Doxorubicin)
- GI toxicity (colitis)
- Vesicant
128
When is the nadir for anti-tumor antibiotics and WBCs?
- 7-10 days
129
Cumulative cardiac toxicity of doxorubicin
- Irreversible
- 180-240 mg/M^2
- Consider with pre-existing cardiac disease
130
How many doses is typically the max dose for doxorubicin?
- 6 doses generally
131
GI toxicity of doxorubicin - what form of toxicity?
- Colitis (hemorrhagic)
132
Doxorubicin effect on veins
- Vesicant
- SEVERE tissue reaction is extravasated
- Can lead to amputation of a limb
- Do NOT put it on a pump; let it drip
- "One-stick" per vein
133
Clinical use of antitumor antibiotics (e.g. doxorubicin)
- Lymphoma protocol component
- Used for sarcomas (best bet)
- Doxorubicin has high activity against a variety of tumors
134
Relative cardiotoxicity and efficacy of newer antitumor antibiotic analogs
- Less cardiotoxic
| - Also less efficacious
135
Bleomycin
- Antitumor antibiotic used for electrochemotherapy
136
MOA of platinum compounds
- Intra-strand cross-link of DNA interfering with RNA synthesis and DNA replication
137
Examples of platinum compounds
- Cisplatin
| - Carboplatin
138
Relative dosing of cisplatin and carboplatin
- Cisplatin has MUCH MUCH lower dosing than carboplatin
139
Which of the platinum compounds tends to be used more?
- Carboplatin
140
Cisplatin toxicity with BAG
- BAG
- HIGHLY HIGHLY emetogenic
- Patients require anti-emetics, always pre-treatment
141
BAG Toxicity of Carboplatin
- BAG
- Less emetogenic than cisplatin
- Bimodal nadir of carboplatin at 6 and 15 days
142
Monitoring CBC with carboplatin
- Due to bimodal nadir of carboplatin, check at 1, 2, and 3 weeks
143
Relative nephrotoxicity of carboplatin and cisplatin
- Cisplatin has high nephrotoxicity
| - Diuresis pre, during, and post treatment
144
Respiratory toxicity of cisplatin vs carboplatin
- Fatal pulmonary edema in cats
| - Carboplatin is much safer in cats
145
General toxicities of cisplatin and carboplatin rehash :)
1. BAG
2. Nephrotoxicity
3. Lung toxicity
4. Ototoxicity
146
Cisplatin and carboplatin tumor types
- Cisplatin was agent of choice for osteosarcoma but largely replaced by carboplatin
- Carcinomas
- Intralesional in equine sarcoids with beads
147
Antimetabolites MOA
- Interfere with purine and pyrimidine synthesis and incorporation into DNA
148
Examples of anti-metabolites
- Methotrexate
- Cytosine arabinoside
- 5-fluorouracil (5-FU)
- Azathiprine
149
Toxicity of Methotrexate (antimetabolite)
- BAG
| - NAdir around 1 week
150
Drug interaction potential with methotrexate
- highly protein bound - drug interaction potential
151
General length of action of antimetabolites
- Most are phase specific
| - Short acting
152
5- fluorouracil toxicity (antimetabolite)
- BAG (white count)
| - Central neurotoxicity (fatal in cats)
153
Aazthioprine toxicity
- BAG (lower frequency in dogs than other agents)
| - Avoid in cats (myelosuppression)
154
Cytosine arabinoside toxicity
- BAG nadir 1-14 days
155
Tumor type for methotrexate
- Component of older protocol for lymphoma
| - Not used that often anymore
156
Tumor type for 5-fluorouracil (5-FU)
- Carcinomas
157
Clinical use for azathioprine
- Immune mediated diseases
158
Clinical use for cytosine arabinoside
- Lymphoma in horses (arabinoside for Arabian horses)
- Canine non-infectious encephalitis
- Acute leukemia
159
Mechanism of action of enzymes like L-asparaginase
- Inhibits protein synthesis
| - Depriving tumor of asparagine
160
Example of anti-tumor enzyme
- L-asparaginase
161
Toxicity of enzymes like L-asparaginase
- Allergic reactions
- Relatively bone marrow sparing (unless in combination with vincristine)
- Pancreatitis
- Sometimes vomiting
162
What to do with a patient vomiting on L-asparaginase?
- Take more seriously than you might with other drugs
| - Could be pancreatitis
163
What history might preclude use of enzymes like L-asparaginase?
- Pancreatitis
164
What to do for prevention of allergic reactions with L-asparaginase?
- Pretreat with antihistamines +/- glucocorticoids
165
Clinical use of L-asparaginase
- Lymphoma
166
Route of L-asparaginase
- SC only
| - NOT IV (anaphylaxis risk)
167
Mechanism of NSAIDs for use with tumors
- COX-2 overexpressed in many tumors
- May be a growth factor?
- NSAIDs enhance apoptosis
- Decrease tumor invasiveness
- Block angiogenesis
168
Piroxicam
- NSAID
- They used to use this
- Not COX-2 selective, so more chance for GI ulceration
169
Toxicity of piroxicam
- GI ulceration
| - renal
170
Tumors to treat with piroxicam or other NSAIDs (deracoxib)
- Transitional cell carcinoma
| - Palliation of other tumor types
171
What might be a better NSAID and why for treating transitiona cell carcinoma in dogs?
- Deracoxib
- COX-2 selective, so less likely to cause ulceration
- Same chance of renal injury
172
Tyrosine kinase inhibitors MOA
- Inhibit cell signaling (proteins involved in cell replication)
173
Examples of tyrosine kinase inhibitors
- Toceranib phosphate (Palladia)
174
Indication for Toceranib phosphate
- 1st FDA approved drug for treating cancer in veterinary patients
- Grade II and III mast cell tumors
175
Route for tyrosine kinase inhibitors
- Tablets
176
What drug should you avoid with tyrosine kinase inhibitors?
- NSAIDs
| - VERY protein bound, which will change the metabolism of NSAIDs
177
Masitinib drug type
- Tyrosine kinase inhibitors
178
Masitinib use in the US
- Currently off market in US
- Was indicated for grade II and III mast cell tumors
- similar to toceranib
179
Adverse effects of Tyrosine Kinase inhibitors (Toceranib)
- Neutropenia (Check CBCs once a week)
- GI ulceration (Avoid NSAIDs)
- Vasculitis (thromboembolic disease)
- Protein losing nephropathy
180
How long do animals stay on tyrosine kinase inhibitors?
- For life
| - making cancer behave
181
MOA of Canine Melanoma vaccine
- DNA vaccine
- Human tyrosinase
- Tyrosinase is present on the surface of melanoma cells
- Triggers immune response
182
Approval of Canine Melanoma vaccine
- USDA approved
- Stage II or III melanoma in conjunction with standard treatment (surgery or radiation therapy) for local disease
- Proprietary injection device
183
Dosing protocol for ONCEPT or the canine melanoma vaccine
- 2 weeks apart + 6 month booster
184
Why are the results for the ONCEPT/Canine melanoma vaccine so equivocal?
- Initial efficacy study compared to historical controls
185
Adverse effects of ONCEPT/canine melanoma vaccine
- Injection site pain
- Fever
- Hypersensitivity (rare)
- Localized vitiligo
186
Cons of the canine melanoma vaccine
- Expensive
- At least two studies done recently showed that Stage II and Stage III didn't have a difference in progression-free survival
- Other therapies might be better now
187
Pros of canine melanoma vaccine
- Pretty safe
| - Might work for some dogs
188
Definition of metronomics
- Low doses more frequency to cut down on some negative side effects
189
Metronomics - which drugs used with metronomics?
- Alkylating agents
| - Oral
190
Benefits of metronomics?
- Cuts down on negative effects
| - may have anti-angiogenic effects
191
Metronomic lomustine study
- discontinued because of toxicity
| - GI, liver toxicity, azotemia, thrombocytopenia, neutropenia, etc.
192
Metronomic cyclophosphamide toxicity
- Greater incidence of cystitis potentially
| - Did seem to make it past median return time for tumors in combo with piroxicam
193
How to manage nausea/vomiting in patients on anticancer drugs?
- Maropitant (Cerenia)
- Ondansetron
- Butorphanol (specifically prior to cisplatin)
194
Which anti-cancer drug can lead to diarrhea?
- Doxorubicin
195
Doxorubicin diarrhea - what to do?
- She thinks it's a result of giving them a lot of cookies
- If you give a controlled diet, that might help control
- Loperamide (MUST KNOW MDR1 status)
- Morphine
- Metronidazole
- Imodium or a high fiber diet
196
What therapies can be given to dogs who experience diarrhea on anticancer drugs?
- Morphine (particularly dogs that are painful from severe tenesmus)
- Metronidazole (due to bacterial overgrowth)
- Also could try high fiber diet or imodium (loperamide
197
GI complications secondary to mast cell tumors
- Excess histamine
198
Treatment for GI complications secondary to mast cell tumors
- Prevent GI ulceration with H2 blockers (famotidine or ranitidine)
- PPI (omeprazole)
199
Managing neutropenia
- Treatment depends on grade and presence of fever
200
Treatment for grade 1-2 neutropenia (afebrile)
- oral antibacterial agent
- Selection based on most likely source of infection
- Some people might not put them on antibiotics and tell the owner to monitor temperature
201
Grade 3-4 neutropenia (afebrile) in cancer patient
- Oral antibacterial agents (Clavamox or cephalexin)
| - 4 quadrant coverage
202
Patient with any degree of neutropenia who is febrile?
- Parenteral or injectable medications
| - Might be septic
203
rhG-CSF usage
- Most effective if given PRIOR to treatment with cytotoxic
- I think it's an antibody thing
- Antibody production (rhG-CSF) can cause prolonged CSF
204
How long to keep a neutropenic cancer patient in the hospital for?
- NO LONGER THAN WHAT IS NECESSARY
- Keep them until their temperature goes down and they take oral medications
- Don't wait until WBC increases, as it's dangerous for them to be in hospital
205
Which chemo treatments are substrates for P-glycoprotein?
- Vincristine and vinblastine
- Doxorubicin (antibiotics)
- Paclitaxel
206
What side effects are more likely in dogs with MDR1 mutation?
- Bone marrow suppression
- Thrombocytopenia
- GI
- Neuropathy
207
Are dogs with MDR1 heterozygote mutation capable of being sensitive to chemotherapeutic drugs?
- YES
208
Why are dogs with MDR1 sensitive to chemotherapeutic drugs?
- Not a blood-brain-barrier problems
- More like P-gp is needed for biliary excretion of vincristine, vinblastine, doxorubicin, and paclitaxel
- They will circulate longer
209
Clinical implications for treating dogs with cancer with possible MDR1
- Test ALL herding breeds
- Test mixed breed dogs
- MDR1 mutant/mutant dogs have SEVERE adverse effects
210
Dose reductions for an MDR1 mutant/mutant?
- 50% decrease
211
MDR1 reductions for an MDR1 heterozygote?
- 25%
