Oncology Flashcards
1
Q
When preparing, administering, or disposing of chemotherapeutics, or when cleaning up waste from patients that have received chemo, what PPE is recommended?
A
- Chemotherapy rated double gloving
- Long sleeved, coated impermeable gowns with back closure
- Eye/face shield
- Shoe and hair coverings to maintain sterility (if needed)
- Respirator if there is potential for aerosolization
2
Q
Animals receiving chemo at home should not be allowed to urinate/defecate in community areas, areas where children may be exposed, or areas that are difficult to clean for how many hours after administration?
A
48 hours
3
Q
What is the mechanism of action of alkylating agents?
A
- Bind to DNA strands and insert an alkyl group, which creates cross links in DNA => strand breaks
- Act in all phases of the cell cycle
4
Q
Name 5 alkylating agents
A
- Cyclophosphamide
- Chlorambucil
- Melphalan
- Lomustine (CCNU)
- Mustargen
- Procarbazine
- Dacarbazine
5
Q
What is the mechanism of action of mitotic inhibitors? Name 3
A
- Inhibit the assembly (vinca alkaloids) or disassembly (paclitaxel) of the mitotic spindle - arrest cell division in metaphase
- Vincristine, vinblastine, vinorelbine
6
Q
What is the mechanism of action of platinum compounds? Name 2
A
- Create cross links in DNA (like alkylating agents)
- Cisplatin, carboplatin
7
Q
Why is cisplatin fatal when given to cats?
A
Causes pulmonary edema
8
Q
What is metronomic chemotherapy?
A
Uses small doses of chemotherapy drugs frequently (daily or EOD) rather than conventional chemotherapy, which uses maximum tolerated doses at intervals of weeks
9
Q
What is the mechanism of action of metronomic chemotherapy?
A
- Anti-angiogenic (targets tumor endothelial cells)
- Immunomodulatory (inhibits Tregs)
- NOT cytotoxic, like conventional chemo
10
Q
After giving chemotherapy, the patient’s neutrophil count should be checked at the expected nadir or before the next dose of myelosuppressive chemotherapy. If the neutrophil count is <1,000, what should be done?
A
Patient is afebrile, healthy
- Consider prophylactic antibiotics at home
- Reduce future dose by 25%
Patient is febrile or sick
- Hospitalize for IV antibiotics, fluids - treat for sepsis
11
Q
If the neutrophil count is 1,000-3,000, what should be done?
A
Delay scheduled chemotherapy until the neutrophil count is >3,000. Recheck CBC in 3-7 days
12
Q
One common mechanism of tumor resistance to chemotherapy is the P-glycoprotein transmembrane pump, which can efflux chemo out of the tumor cells. What chemo drugs are NOT substrates for this pump and will still be effective?
A
Alkylating agents - mainstay of treatment for patients with this type of resistance
13
Q
What oral chemotherapy drug is used for the treatment of multiple myeloma?
A
Melphalan
14
Q
If vincristine is given outside of the vein, what should be done?
A
Dilute and WARM compress
15
Q
What is the mechanism of action of doxorubicin and mitoxantrone?
A
Inhibit topoisomerase II => inhibition of DNA synthesis
S phase specific
16
Q
If doxorubicin is given outside of the vein, what should be done?
A
COLD compress
17
Q
What chemotherapeutic can cause a red color in the urine up to 2 days post-administration?
A
Doxorubicin
18
Q
What chemotherapy drug can cause anaphylaxis within 30 minutes of administration and the patient should be pretreated with dexamethasone and/or Benadryl?
A
L-asparaginase
19
Q
Name 3 chemotherapeutics that cross the blood brain barrier
A
CCNU, procarbazine, cytarabine
20
Q
What drug can be given to reduce cardiotoxicty from doxorubicin? How does it work?
A
Dexrazocane (Zinecard)
21
Q
What is the mechanism of action of L-asparaginase?
A
Catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives myeloproiferative cells of circulating asparagine because they cannot synthesize it on their own, which leads to cell death
22
Q
What detoxification system is upregulated by many cancer cells to remove chemotherapeutic drugs?
A
Glutathione system
23
Q
What is multidrug resistance-related protein?
A
Protein that excretes detoxified products of the glutathione system - unregulated in some cancer cells
24
Q
What cell type expresses CD1?
A
Antigen presenting cells - useful for diagnosing histioproliferative disorders
25
Describe the staging system for lymphoma
- Stage 1: single LN
- Stage 2: multiple LNs in a regional area
- Stage 3: generalized LN involvement
- Stage 4: Liver and/or spleen involvement (with OR without LN involvement)
- Stage 5: bone marrow or blood involvement and/or any non-lymphoid organ (with OR without any of the other stages)
Substage a: no clinical signs
Substage b: clinical signs
26
Describe acute radiation toxicity. What types of tissue are most affected?
- Affects rapidly proliferating tissues (skin, mucous membranes)
- Generally reversible changes that occur during or shortly after therapy
- Increase with dose, dose rate, and dose per fraction
27
Describe late radiation toxicity
- Affects tissues that have limited to no renewing capabilities (bone, nerve, muscle)
- Occurs 3-6 months after radiation
- Severity dependent on dose per fraction
- Progressive and irreversible changes
28
What radiation protocols are more likely to cause acute toxicity? Late toxicity?
Acute toxicity - definitive intent protocols
Late toxicity - palliative intent protocols
29
What is the typical schedule and dosing for definitive intent radiation?
- Large number of fractions with a low dose/fraction
- Goal is to achieve long term control while limiting late toxicity
30
What is the typical schedule and dosing for palliative intent radiation?
- Fewer number of fractions, but a high dose per fraction
- Intent is to improve QOL (improve function, decrease pain/bleeding)
31
In a study of malignant solid tumors treated with palliative intent radiation, what tumor types had the best overall response rate? What was the overall response rate?
- Sarcoma (87%), primary bone tumors (85%), melanoma (73%)
- Overall response rate 75%
32
In a study of malignant solid tumors treated with palliative intent radiation, what was the MST? What factors influenced MST?
134 days - did not vary with tumor location, but dogs that had a positive clinical response or maintained stable disease after radiation had longer MSTs
33
In a study of malignant solid tumors treated with palliative intent radiation, what percent of dogs developed acute toxicity? Late toxicity?
- Acute - 55% (dermatitis, alopecia, mucositis most common)
- Chronic - 12% in dogs that lived at least 3 months - neuropathy, blindness, laryngeal paralysis, etc
34
What is thought to cause feline injection site sarcomas?
Pathogenesis not fully known, but it is thought that local irritation (especially from adjuvants) stimulates fibroblasts - chronic inflammation leads to malignant transformation
35
What vaccines are more at risk of inducing feline injection site sarcomas?
Adjuvanted, killed vaccines (rabies, FeLV), although any vaccine and injections of long acting drugs (glucocorticoids, etc) can
36
What temperature of vaccine is more likely to induce feline injection site sarcomas?
Cold vaccines - bring to room temperature for 15 minutes before injection
37
What are the most common presenting characteristics of dogs with B cell CLL?
Peripheral lymphadenopathy or splenomegaly (50%)
Anemia (26%)
38
English bulldogs are at increased risk of B cell CLL and have a unique presentation. What is it?
- Younger (6 yrs vs 11 yrs)
- Lower class II MHC and CD25
39
Over 50% of gliomas occur in what dog breeds?
Brachycephalics
40
What are the diagnostic criteria for B cell CLL?
- Usually >5000 to 6000 lymphocytes/uL in the blood
- B cell expansion by immunophenotyping
- Small cell morphology
41
What dog breed has a shorter survival time with B cell CLL than other breeds? Why?
Boxers - BCLL in these dogs preferentially rearrange unmated immunoglobulin heavy variable region genes - poorer outcome in people
42
What are negative prognostic indicators in B cell CLL cases?
- Ki67 - greater than 40% of Ki67 expression had a shorter MST (173 days vs not reached)
- High lymphocyte count: >60,000 lymphocytes
- Clinical signs at presentation
43
Describe the staging scheme for canine splenic hemangiosarcoma
- Stage I: <5 cm diameter tumor, no mets
- Stage II: >5cm diameter tumor OR evidence of rupture, +/- regional LN involvement
- Stage III: distant mets
44
In dogs with stage II splenic hemangiosarcoma, what histologically determined score correlated with survival?
Mitotic index: <11 mitoses/10 hpf did better
45
Of dogs undergoing splenectomy for nonruptured splenic masses or nodules (no hemoperitoneum), what percent were benign?
70%
46
Are thoracic radiographs sensitive or specific for heart base masses?
Specific, but not very sensitive
47
What percent of cats treated for small cell GI lymphoma develop large cell GI lymphoma? When does it occur?
10% - developed large cell 540 days after small cell diagnosis
48
What clinicopathologic findings were more common in cats with large cell vs small cell GI lymphoma?
Lower hematocrit, albumin, and total protein - cats with small cell lymphoma that develop these signs should be screened for large cell
49
What was the MST for feline large cell GI lymphoma?
25 days
50
What subset of dogs with mammary carcinoma benefit from OHE at the time of tumor removal?
Dogs with high peri-surgical serum estradiol concentrations or expression of estrogen receptors on tumor IHC
51
What dog breed may be more predisposed to pulmonary histiocytic sarcoma?
Miniature schnauzers
52
What are the clinical findings in dogs with doxorubicin induced cardiotoxicity?
- Decreased systolic function, resembling DCM
- Arrhythmias
53
What factors were associated with doxorubicin induced cardiotoxicity in the JVIM paper?
- Higher cumulative dose (144 vs 121 mg/m2)
- Higher body weight
- Decreases in fractional shortening after 5 doses
- Development of VPCs
- Boxers
54
In dogs with previously untreated, peripheral nodal lymphoma treated with prednisone alone, what was the MST? What factors were associated with survival
- 50 days
- Substage (a vs b) and immunophenotype
55
In dogs with lymphoma, what tumor mutation was associated with decreased survival time?
p53 mutation: 67 days vs 264 days
56
What sample type yielded the best sensitivity and specificity for PARR in canine lymphoma?
FNA (100% S&S) > FFPE > flow cytometry pellets
57
Bernese Mountain dogs with what other condition were at increased risk of developing histiocytic sarcoma? What decreased their risk?
- Orthopedic condition = increased risk
- Administration of anti-inflammatory meds = lower risk
Inflammation may be a risk factor?
58
In dogs with genitourinary carcinoma treated with NSAIDs, mitoxantrone, and RT, what factors influenced survival?
- Shorter survival in dogs with moderate to severe clinical signs
- Shorter in dogs with prostatic involvement
59
n dogs with genitourinary carcinoma treated with NSAIDs, mitoxantrone, and RT, what percent developed permanent urinary incontinence? When did it develop?
31% - median of 70 days post-irradiation
60
What detergent is most effective for dispersing oncology drug spills?
Bleach (hypochlorite)
61
What stages of the cell cycle do the following chemotherapy drugs work on:
a) Antimetabolites
b) Alkylating agents
c) Cross-linking agents
d) Toipomerase inhibitors
e) Antimicrotubule agents
f) Signal transduction inhibitors
a - d = S-phase (DNA replication)
e = mitosis (M-phase)
f = generally G1 (growth 1 phase)
62
MoA alkylating agents
Cross-linking of DNA leading to strand breaks by covalently binding alklyl groups to macromolecules within the cell
63
MoA anti-tumour antibiotics
Inhibition of toipoimerases and other mechanisms which interfere with DNA synthesis
64
Mitotic inhibitors MoA
Inhibit assembly of the mitotic spindle
65
Platinum compounds MoA
DNA cross linking
66
Anti-metabolites MoA
Incorporation into DNA interferes with DNA synthesis
67
Examples of the following oncologic drugs:
a) Alkylating agents
b) Anti-tumour antibiotics
c) Mitotic inhibitors
d) Platinum compounds
a) Cyclophosphamide, chlorambucil, melphalan, lomustine, procarbazine
b) Doxorubicin, mitoxantrone
c) Vinca-alkyloids
d) Cisplatin/carboplatin
Essentially if its not an anti-tumour antibiotic, mitotic inhibitor or platinum compound it is an alkylating agent
68
For Taxanes (Paclitaxel and Docetaxil) outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) anti-microtubule agents (M-phase specific)
b) Prevention of tubule organisation
c) Hypersensitivity reactions, myelosupression, diarrhoea
d) Hepatic metabolism - biliary excretion
e) Anti-histamines given prior to administration
69
For Vinca Alkaloids outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) anti-microtubule agents (M-phase specific)
b) Binding to tubulin prevents microtubule assembly
c) Tissue vesicants - HEAT and HYALURONIDASE (also topical DMSO and flucinolone and flunixin meglumine), peripheral myelopathies, alopecia, myelosupression, diarrhoea
d) hepatic metabolism and biliary excretion
e) Care with MDR1
70
For Cyclophasphamide outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (nitrogen mustard)
b) Cross linking of DNA through insertion of an alklyl group
c) DLT include myeosupression (7 days), sterile haemorrhagic cytitis (prevented with frusemide), gastrointestinal signs and alopecia
d) Hepatic metabolism and renal excretion
e) Sterille haemorrhagic cystitis is a result of metabolism to acrolein which is directly toxic to the bladder mucosa. Specific treatments include pentosan sulfate, DMSO, oxybutinin and NSAIDs
71
For Chlorambucil outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (nitrogen mustard)
b) Cros links DNA through insertion of an alkyl group
c) DLT - myelosupression which occurs after 2 - 3 weeks. Cerebellar toxicity, alopecia and GIT signs
d) hepatic metabolism and renal excretion
72
For Dacarbazine and Procarbazine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) Metabolised to MTIC which then methylates guanine
c) Cannot be used in cats as they don't convert enough to the active form. DLT is GI side effects. Is also a vesicant.
73
For Ifosphamide outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent (itrogen mustard) - similar to cyclophosphamide.
b) Insertion of alklyl group
c) DLT = myelosupression, can also cause GI and bladder mucosal changes. It should be administered with mesna and fluids.
74
For Lomustine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) as for all alkylating agents
c) DLT is myelosupression which may occur after 7 - 10 days. Other side effects include hepatotoxicity and pulmonary fibrosis (cats).
d) Hepatic metabolism and renal excretion
e)
75
For Melphalan outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) as for all
c) Myelosupression, GI, pulmonary infiltrates and fibrosis have also been described.
d) 25 - 30% is excreted unchanged in the urine but it spontaneously degrades to inactive metabolites.
76
For Streptozoocin outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Alkylating agent
b) It is selective for beta cells (and the kidney) as it requires uptake via GLUT2.
c) DLT is nephrotoxicity but can also cause hepatotoxicity
77
For Actinomycin D outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) Complexes DNA and inhibits RNA synthesis
c) Myelosupression, GI signs and vesicant (use cold for treatment)
78
For Doxorubicin outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) Complexes DNA, generates free radicals and inhibits toipoimerase activity.
c) DLTs = myelosupression (7 - 10d nadir) and GI toxicity (may result in colitis)
Cardiac toxicity can be acute (arrythmais) or chronic (DCM phenotype).
It is also a vesicant, the treatment is COLD, DMSO and dexraxozane
Nephrotoxic to cats
79
Dexraxoxone - how does it work?
Dexrazoxane is hydrolyzed to an active metabolite that chelates intracellular iron, which is believed to prevent the formation of an anthracycline-iron complex free radical that is thought to be the primary cause of anthracycline-induced cardiomyopathy and extravasation injury.
80
For Mitoxantron outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-tumour antibiotic
b) It is essentialyl the same as doxoruicin (synthetic analogue) so complexed DNA generates free radicals and inhibits toipoimerase.
c) It does not cause cardiotoxicity, can cause seizures in cats,
81
For Cytarabine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Inhibits DNA polymerase alpha and incorporation into DNA also results in apoptosis
c) Myelosupression and GIT signs
82
For Gemcitabine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
Anti-metabolite that inhibitis DNA polymerase. It has not been extensively used so little other information.
83
Methotrexate MoA
Inhibits dihydrofolate reductase and other folate metabolic pathways => inhibiting purine synthesis. It is not used much due to side effect profile.
84
For Rabacfosadine outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Guanine nucleotide analogue
c) * GI
* Myelosuppression
* Hepatotoxicity
* Proteinuria
* Dermatologic toxicity
* Idiosyncratic pulmonary fibrosis (irreversible) - should not be used in patients with IPF
It is a vesicant which can be treated with cold and aspiration of the area
85
For 5-FU outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Anti-metabolite
b) Uracil analogue
c) Myelotoxicity, GI toxicity, Neurotoxicity, Ingestion of topical cream can be fatal
86
For L-asparaginase outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) This is a miscellaneous drug.
b) Hydrolyses L-asparaginine to L-asparanagic acid. This is effective in cells that lack asparagine synthase (e.g. lymphocytes) which inhibits purine metabolism.
c) The main concern is that anaphylaxis can occur with repeat dosing. Rare side effects include pancreatitis, myelosupression and DIC
d) The body will quickly develop antibodies to L-asp so it becomes ineffective quickly.
87
For platinum compouds (cisplatin/carboplatin) outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Platinum based compounds
b) Covalent binding and cross-linking of DNA
c) Myelosupression, GI, renal (cisplatin only), pulmonary oedema and vasculitis (cats), hepatotoxicity, neuropathies and ototoxicity is also possible
88
For Hydroxyurea outline the:
a) Drug class
b) MoA
c) DLTs/side effects +/- treatments
d) Useful PK/PD to know
e) Notes
a) Misc
b) inhibits ribonucleoside reductase leading to a reduction in available RNA pools for protein synthesis
c) * GI, Myelosuppression, Pulmonary fibrosis, Methoglobinaemia (cats), Claw detachment (dogs)
89
What flow cytometry markers identify T-cells generally and more specifically?
CD3 & 5 identify T-cells generally
CD4+ and CD8+ identify specific subtypes
90
What flow cytometry markers identify B-cells?
CD21
Also:
- CD22
- CD79a
- Pax5
91
Which flow cytometry markers identify lymphoid cells?
CD45, CD11a
92
What flow cytometry marker differentiates immature (blasts) from matture lymphoid populations?
CD34
93
What cell types does MHC expression identify?
Monocytes, B-lymphocytes and T-cells
94
Which cell markers identify monocytes AND neutrophils?
CD18
95
Which cell marker identifies monocytes
CD14
