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ECVIM Certifier > Onco > Flashcards

Onco Flashcards

1
Q

Six hallmarks of cancer?

A 
Self sufficiency in growth signals
Evade apoptosis
Sustain angiogenesis
Insensitivity to active growth signals
Tissue invasion and mets
Limitless replicative potential
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2
Q

Alkylating agents?

A

Cross link DNA
Strand breaks
Cross resistance between different alkylating agents and other classes of drugs

Cyclophosphamide, chlorambucil, melphalan, lomustine, procarbazine

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3
Q

Anti tumour antibiotics?

A

Anthracyclines
DNA intercalation, interfere with topoisomerases
Cross resistance with others in class and some other classes esp mitotic inhibitors
Substrates MDR

Doxorubicin, mitoxantrone, dactinomcin, bleomycin

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4
Q

Mitotic inhibitors?

A

Inhibit assembly (vinca alkaloids) or disassembly (paxlitaxel) of mitotic spindle

Vincristine vinblastine vinorelbine

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5
Q

Platinums?

A

Cross link DNA, similar mechanism alkylating agents, no cross resistance other classes of drugs

Cisplatin carboplatin

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6
Q

Antimetabolites?

A

Analogues of normal metabolites incorporated into DNA, interfere with enzyme activity/transcription/translation. Sig tox low efficacy @ vet dose.

Gemcitabiine (infusion rate/time imp).

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7
Q

TKI?

A

Toceranib/masitinib

Toceranib needs lower dose than label

c-kit and tumour angiogenesis with VEGF. Immunomodulatory.

Toceranib:
Reversible competitive ATP binding to prevent phosphorylation/downstream signalling of receptor tyrosine kinases. VEFGR2/3, PDGFRalpha/beta, KIT , CSF1R, FLT3, RET = targets

Benefit also 75 % solid tumours

Synergistic with vinblastine and RT
Immunomodulatory (Treg decreased), increased IFNgamma

Probably no benefit in microscopic dz without tumour driver like mutant KIT (MCTs)

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8
Q

Tumour cell resistance?

A

Due to high mutation rate after drug exposure

Combination might overcome resistance - but more tox normal cells?

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9
Q

Myelosuppression potential of chemo drugs?

A

High - doxo, lomustine, cyclophosphamide, carbo, vinblastine, mitox

Medium - vinc, chlorambucil, melphalan, methotrexate, cisplatin, hydroxyurea, 5-fluorourracil

Low - steroid, L-aspar, lower dose zinc, bleomycin, streptozocin

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10
Q

Metronomic chemo?

A

Mainly antiangiogenic (target tumour endothelial cells) and immunomodulatory (inhibit Treg)

Cyclo, lomustine, chlorambucil

COX inhibitors increased antiangiogenic and immunomod effect

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11
Q

Chemoprotection?

A

Mesna - less cyclo/ifosfamide bladder tox by binding metabolites in urine

Dexrazoxane - protect cf doxo cardiotox and help with extravasation

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12
Q

Overall response rate and clinical benefit?

A 
ORR = CR + PR 
CB = CR + PR + SD
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13
Q

What cells as resistant to l-asparaginase?

A

Those with asparagine synthase

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14
Q

Multiple drug resistance?

A

P glycoprotein pump mediated

Level and prevalence increases with chemo

Anthracycline, mitotic inhibitors etc

Alkylating agents NOT P glycoprotein substrates

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15
Q

Post chemo neutrophil count reactions?

A

> 3 no change
1 - 3 delay chemo
< 1 - febrile, ABs and hosp, afebrile, monitor/reduce dose 25 %, prophylactic AB

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16
Q

Late radiation effects?

A

> 6m
Heart, lung, kidney, nerves brain, bone, muscle
Slowly proliferating/non-renewing tissues

Progressive/irreparable

Vascular damage, fibrosis, necrosis, chronic inflam and loss of normal tissue stem cells

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17
Q

Use of toceranib in MCT?

A

Unrescectable grade 2/3 MCT

60 % overall response 2x as likely if KIT mutation and more if no LN involvement

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18
Q

Toceranib dose?

A

2.4 - 2.9 EOD

Reduced adversed effects at this dose

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19
Q

Masitinib?

A

KIT, PDGFR, cytoplasmic kinase Lyn

MCT w/ KIT mutation

Higher response primary cf relapsed dz

Imatinib response in cats with MCT and KIT mutation

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20
Q

When to use mg/kg chemo dosing?

A

Small patients doxo and carbo

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21
Q

What drugs cause nadirs not at 7 days?

A

Carbo 14d dog, variable cat (14 - 25)

Lomustine cats unpredictable, 7 - 28d

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22
Q

Vinc + laspar?

A

More BM supp

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23
Q

MDR1 drugs?

A

ABCD1-1 delta gene mutation

Vinca alkaloid, doxorubicin, mitoxantrone, taxanes, dactinomycen

GSD collies

Does reduction for affected individual, problem if homozygous

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24
Q

When not to give myelosupp drug?

A

Plt < 75

Neut < 2

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25
Q

Grades of white cell supp?

A

1 - neut > 1.5, pot > 100, pcv > 30/25
2 - 1-1.5, 50 - 99, 20-30/20-25
3 - 0.5-1, 25-49, 15-20/15-20
4 - < 0.5, < 25, <15/<15

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26
Q

Drugs associated with cumulative thrombocytopenia?

A

Lomustine, melphalan, chlorambucil

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27
Q

Perivascular extravasation drug issues?

A

Irritants -platinums, dacarbazine, mitoxantrone, taxanes

Vesicants - vinca alkaloids, anthracyclines, dactinomycin, meechlorethamine

Vina alkaloid - warm compress, DMSO, hyaluronidase

Doxo/epirubicin/dactinomycin - cold compress, dexrazocane (iron chelator), DMSO

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28
Q

Liposomal doxorubicin?

A

Palmar-plantar erythrodysesthesia

Reduced by pyridoxine (B6) admin

Less cardio toxicosis

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29
Q

Mechanism of GI side effects chemo drugs?

A

CRTZ (quick)
Enterocyte in crypts (1-5d)
TKI direct GI irritation
Vinc - ileus (enteric neurotox) - can replace with vinblastine

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30
Q

Maropitant and doxo?

A

Sig decrease both V+ and D+

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31
Q

Doxo cardiotoxicosis?

A

Acute - transient vent arrhythmia d/t histamine/catecholamine release

Cumulative - oxidative sarcoplasmic reticulum injury, decreased contractility +/- arrhythmia, CHF

> 180 - 240mg/m2
Use less cardiotox or give dexrazoxane after max dose

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32
Q

Lomustine hepatotoxicicosis?

A

ALT inc 86 %
Cumulative, often irreversible
Acute liver failure can occur after single tx

Delay/discontinue if ALT increases > 3x RI

Less common in cats

Other drugs increasing ALT:
Streptozoocin
TKI

Other:
Vinc biliary excretion, avoid/drop dose with cholestasis

33
Q

Chemo neurotox?

A

5-FU contraindicated cats
ABCB1-1delta mutation
Chlorambucil myoclonus/seizures

34
Q

Nephrotoxic chemo drugs?

A 
Cisplatin (don't use in cats pulm oedema)
Ifosfamide (dog and cat)
Streptozoocin (dog)
Doxo (cats)
Lomustine (dog)
NSAIDs (don't combo with cisplatin)
Bisphosphonate
TKI PLN (10 % - reversible)
Carbo cats, ideally GFR individualisation
35
Q

Sterile haemorrhagic cystitis?

A

Cyclophosphamide/ifosfamide
Acrolein

Mesna/furosemide reduce risk

Cats lower risk but care FIC

Ifosfamide needs saline diuresis any d/t nephrotox, meson mandatory

Monitor for microscopic haematuria

NSAID/oxybutinin

36
Q

Chemo drug hypersensitivity?

A

L-aspar IgE type 1 - higher risk with higher dose numbers - NEVER IV

Doxorubicin anaphylactoid, histamine from mast cells, non-IgE med, more pronounced faster admin

Cutaneous hypersensitivity inert vehicle mediated - paclitaxel cat/dog, etoposide dog due to cremophor - micellar paclitaxel/subq administration improves

37
Q

Pulmonary tox?

A

Fibrosis bleomycin cumulative

Pulm oedema cat cisplatin

Lomustine pulm hypertensio fibrosis cum dose cat

Rabacfosadine pulm fibrosis

Streptozoocin DM 42 %

Pancreatitis, lameness, muscle cramp TKI

38
Q

Helicobacter in cats?

A

Poss mucosa associated lymphoid tissue lymphoma

Dogs?

39
Q

Most common lymphoma dogs/cats?

A

Dog:
85 % multicentric
70 % B cell

Cat:
Small cell GI - T cell
Intermediate/large cell GI - B cell
Mediastinal Tcell - FeLV (also sometimes multicentric B or T FeLV)
Nasal/peripheral node/laryngeal and tracheal uncommon
Rest rare

Nasal and renal B cell

40
Q

Signalment for lymphoma?

A

Cat - Siamese, esp non-FeLV mediastinal in young <3y

41
Q

Feline large granular lymphoma?

A

FIV/FeLV neg

CD3+/CD8+ T cell or NK cell - SI intraepithelial origin

42
Q

Hodgkin’s?

A

Cats, single or regional LN head/neck, Tcell rich B cell lymphoma

Reed Sternberg like cells

NO FeLV/FIV

43
Q

Lymphoma presentation?

A

Cats more likely to be unwell at presentation

44
Q

Ophthalmic abnormalities lymphoma?

A

1/3-1/2 dog + cat

Retinal haemorrhage, uveitis, ocular infiltration

45
Q

What are markers of proliferation?

A

Ki67
Proliferating cell nuclear antigen (PCNA)
Argyrophilic nucleolar organiser regions (AgNOR)

46
Q

PARR?

A

T cell receptor gene
Immunoglobulin receptor gene

70 - 90 % sens dog, less cat
False neg - null cell, incorrect PCR primer
False pos - ehrlichia, lyme around 5 %

Flow cytometry might be superior

47
Q

Lymphoma response/remission/MST dog?

A

CHOP: 90 %, 8m, 12m
20 - 25 % alive 2y

Doxo/pred: 70 % response 5m 7m

48
Q

Pred and chemo response?

A

Pretx pred decrease survival time, response rate, shorter remission if real chemo added

49
Q

Lymphoma response/remission/MST cat?

A

COP/CHOP might be no different and doxo not effective as single agent

Less remission response and survival cf dogs for intermediate and high grade

50 - 80 %, 4-6m, 6-8m

If complete response 30 - 40 %live 2y

50
Q

What to do when lymphoma relapses?

A

If > 2m since stop chemo, reinduction

High response, less response time

Reinducation failure - rescue 40 - 90 % response, 1.5-2.5m duration

51
Q

Indolent lymphoma?

A

T cell GI (MST 3y)
Dog marginal zone/mantel cell/T zone lymphoma

Single agent chlorambucil/cyclophosphamide and pred

Splenectomy/solitary node resection

52
Q

BBB chemo?

A

Cytarabine crosses

Nitrosureas

L-aspar DOESN’T but will deplete asparagine in CSF

53
Q

Cutaneous lymphoma?

A

Lomustine, 80 % response, median duration 3m

Less responsive to chemo cf multi centric

54
Q

Prognostic factors canine lymphoma?

A 
B > T (T zone exception)
Stage V
Substage b
High/intermediate grade. high response but shorter MST
Low B cell MHCII expression
Female?
P glycoprotein expression in tumour
Mediastinal - poor response and survival
Diffuse cutaneous and alimentary, hepatosplenic, leukaemia

POS - grade III/IV neutropenia

55
Q

Prognostic factors feline lymphoma?

A 
Pos:
Indolent
Response to tx
Negative retroviral (FeLV probably not FIV)
Early clin stage
Doxo addition?
Nasal and small cell GI

Neg:
large granular

56
Q

Feline ALL?

A

Often FeLV pos and young

57
Q

How many ALL only dx on BM?

A

10 % - no circulating cells

58
Q

Differentiate ALL from lymphoma?

A

LNs not huge
CD34 +
Rapid progression
Poor chemo response

59
Q

CLL features?

A

T cell CD8+
Many granular
Older might be symptomatic

NO assoc FeLV cat

Responsive chemo - use if clin sig problems

Chlorambucil pred MST 1.5y

Becomes resistant/progresses to ALL

60
Q

How to manage chronic myeloproliferative disorders?

A

Hydroxyurea to effect

Exclude secondary causes of BM hyperplasia

61
Q

Hydroyurea SE?

A

Onychomadesis (sloughing of claw/toenail)

62
Q

Acute and chronic myelogenous leukaemia?

A

Acute myeloblast

Chronic neutrophils and late precursors

63
Q

Myeloma related disorders?

A

MM
IgM (Waldesnstrom’s)
Macroglobulinaemia
Solitary plasmacytoma (extraosseous and extramedullary)
Immunoglobulin secreting lymphomas/leukaemia

Hypercalcaemia 15 - 20 % MM dogs, rare in cats

Melphalan/pred

Cat - pred cyclophosphamide vincristine

Cyclophosphamide faster acting

Chlorambucil IgM

64
Q

Multiple myeloma?

A

Light chain - Bence Jones
Heavy chain - heavy chain dz

Cat mostly extra medullary more common than dogs but BM still affected in most

NOT retroviral assoc

IgM = high molecular weight

IgA most common dog, then IgG. Cat IgG

65
Q

What is hyperviscosity syndrome?

A

Magnitude type shape size conc M component

Lesss common cats

Renal dz in 30 - 50 % dogs

66
Q

MM coagulopathy mechanism?

A

M components inhibit platelet agg, stop release platelet factor 3, adsorption minor clotting proteins, generate abnormal fibrin polymerisation, produce heparin like factor, functional calcium decrease

67
Q

Most common melphalan tox?

A

Thrombocytopenia

68
Q

Wat defines MM response?

A

Good = decrease M component 50 %

69
Q

How to treat hypervics?

A

Plasmaphresis

Platelet rich plasma if plt decreased

70
Q

Negative px MM?

A

Hypercalcaemia
Bence jones
Extensive bony lysis

Worse px cat

71
Q

Extramedullary plasmacytoma?

A

Solitary osseous progress MM

Oral or cutaneous in dogs benign

Noncutaneous aggressive, mets common BM/gammopatht not
Colorectal progress more slowly

72
Q

Prognostic indicators MCT?

A 
Neg:
High grade
Node involvement
Subungual, oral, mucous membrane
Mitotic index, AgNOR, PCN, Ki67 pos
Recurrence 
Systemically unwell
Shar pei
Activating ckit gene mutation
Aberrent (cytoplasmic) KIT localisation
73
Q

What chemo drugs work on specific cell cycle?

A

G1: L-aspar
S - methotrexate, hydroxyurea
G2 - cytarabine, bleomycin
M - vinca alkaloids

non cell cycle specific - anthracyclines (but most effective S), alkylating agents

74
Q

Alkylating agents?

A

Non cycle specific
Cross link DNA

Nitrosurea (lomustine) also carbamylate tyrosine residues. BBB penetration.

Nitrogen mustards (cyclophosphamide, melphalan, chlorambucil) no BBB

75
Q

Antimetabolites?

A

Folic acid analogues:(methotrexate) - inhibit enzymes for purine and pyramidine syth
S phase

Pyrimidine analogues:
cytarabine - s phase, penetrate CNS
5-fluorouracil - penetrate CNS , not cell cycle specific

76
Q

Vinca alkaloids?

A

M phase
Prevent polymerisation of microtubules and therefore mitosis
Bile excretion
Vincristine - peripheral neurotox with long term use

77
Q

Antineoplastic antibiotics?

A

Anthracycline - doxo - intercalate between DNA base pairs. biliary excretion

Dactinomycin - bile, same as doxo

Bleomycin - pulm fibrosis as no aminopeptidase for breakdown in lungs, G2

78
Q

L-aspar?

A

G1

Hydrolyses asparagine to aspartic acid and ammonia

No L-asparagine synthase in neoplastic cells

79
Q

Platinum?

A

Crosslink DNA

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