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BVetMed3 POS - Principles Of Oncology > Principles Of Anti-cancer Drug Therapy > Flashcards

Principles Of Anti-cancer Drug Therapy Flashcards

1
Q

What is the goal of chemo in vet species?

A

Palliation/ control rather than cure

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2
Q

What should be considered throughout chemo?

A

QoL

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3
Q

When is chemotherapy indicated?

A

Disseminated disease for chemo-sensitive tumours (e.g. lymphoma)

Adjuvant therapy following sx for highly metastatic tumours (e.g. high grade MCT)

Following incomplete resection
Neo-adjuvant chemo (shrink prior to sx)
Chemosensitive tumours not amenable to sx or XRT

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4
Q

What chemo-sensitive tumours can cause disseminative disease?

A

Lymphoma
Leukaemia / myeloma
Disseminated MCT
Disseminated histiocytic sarcoma

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5
Q

When should chemotherapy NOT be used?

A

Sx or XRT more effective

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6
Q

What are the potential routes of administration for chemo drugs?

A 
oral 
IV 
SC 
intra-cavitary 
Intra-lesional (not common)
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7
Q

When might intra-cavity chemotherapy be indicated?

A

Mesothelioma (cells lining the body cavity)

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8
Q

What cells do most anti-cancer drugs target?

A

Actively dividing cells

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9
Q

How is mitotic index related to the efficacy of chemo?

A

Tumours with a high mitotic index are more likely to be sensitive

Cells in G0 are relatively resistant

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10
Q

Describe the typical growth of tumours

A

Log phase of growth

Plateau phase of growth

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11
Q

During what phase of growth is it best to use chemo?

What is the problem with this clinically?

A

Log phase of growth

Tend to be detected clinically in the plateau phase

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12
Q

Following surgery, when should chemo be started if it is indicated?

Why?

A

As soon as the surgical wound has healed

Need rapidly dividing cells to heal the wound - will be targeted by cytotoxic drugs

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13
Q

How do you quantify the effect of a cytotoxic drug?

A

A given dose kills a fixed percentage of cells

Each treatment reduces numbers by a percentage

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14
Q

What is the MTD?

A

Maximum tolerated dose

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15
Q

Why should you give cytotoxic drugs at pulse dose intervals?

Why should you not leave intervals too long?

A

Allow normal tissues to recover in between doses

DON’t want tumour to regrow

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16
Q

How is toxicity related to the size of an animal?

A

Toxicity often relates more to body surface area than body weight

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17
Q

How do combination protocols compare to using a single agent?

A

MORE EFFECTIVE

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18
Q

What considerations need to be made when devising combination protocols?

A

Use drugs which:
Are effective as a single agent
Have different modes of action and don’t interfere with each other
Ideally act at different stages of the cell cycle
Don’t have overlapping toxicities

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19
Q

What is the COP protocol?

A

Cyclophosphamide
O - vincristine
Prednisolone

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20
Q

What is the CHOP protocol?

A

Cyclophosphamide
H- Doxorubicin
O - vincristine
Prednisolone

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21
Q

What is the LOPP protocol?

A

Lomusine
O- vincristine
Procarbazine
Prednisolone

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22
Q

What can the COP, CHOP and LOPP protocols be used to treat?

A

Lymphoma

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23
Q

What are the phases of chemotherapy?

A

Induction
Maintenance (only in some protocols)
Re-induction
Rescue

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24
Q

Which is the most intense phase of chemo?

A

Induction

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25
Q

What is the rescue phase?

A

Switch to different drugs if the current protocol is not effective

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26
Q

What is metronomic chemotherapy?

A

NSAID plus low dose alkylating agent (cyclophosphamide or chlorambucil)

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27
Q

What are RTKIs?

A

Receptor Tyrosine Kinase inhibitors

Interfere with aberrant cell-signalling in cancer cells

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28
Q

What factors affect the success of chemotherapy?

A

Tumour cell type
Drug distribution
Development of resistance

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29
Q

How can tumour cell type affect success of chemotherapy?

A

Some have intrinsic resistance e.g. many carcinomas, malignant melanoma

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30
Q

How can drug distribution be compromised?

A

Blood supply to neoplasm

Barriers to diffusion e.g. BBB

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31
Q

How can tumours develop resistance?

A

Tumours are genetically unstable

Drug exposure selects for resistant cells

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32
Q

Describe a mechanism for drug resistance.

A

Multi-drug resistance pump - MDR1 gene

Can be upregulated resulting in Doxorubicin and vincristine being pumped OUT

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33
Q

What shouldn’t be used to pre-treat lymphomas before chemo?

Why?

A

Pred

Glucocorticoids can cause MDR1 upregulation

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34
Q

How are alkylating agents cytotoxic?

A

Cross-link DNA and cause strand breakage

Interfere with DNA replication and transcription

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35
Q

When in the cell cycle do alkylating agents act?

A

ALL THE TIME

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36
Q

Which cytotoxic drugs are alkylating agents?

A

Cyclophosphamide
Chlorambucil
Lomustine
Melphalan

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37
Q

What alkylating agents are indicated for lymphoma?

A

Cyclophosphamide
Chlorambucil
Lomustine

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38
Q

Which alkylating agent is indicated for sarcomas?

A

Cyclophosphamide

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39
Q

What is Melphalan indicated for?

A

Myeloma

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40
Q

Which alkylating agent is indicated for brain tumours?

A

Lomustine

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41
Q

How are mitotic spindle inhibitors cytotoxic?

A

Binds to tubulin, interferes with mitotic spindle formation

METAPHASE ARREST

42
Q

At what phase of the cell cycle do mitotic spindle inhibitors act?

43
Q

Give examples of mitotic spindle inhibitors.

A

Vincristine
Vinblastine
Vinorelbine

44
Q

When is vinblastine indicated?

A

high grade MCT

45
Q

What are anti-metabolites?

A

Mimic normal substrates in DNA / RNA synthesis

- inhibit enzymes or make metabolites non-functional

46
Q

What phase of the cell cycle do anti-metabolites affect?

47
Q

Give examples of anti-metabolites

A 
Cytosine arabinoside 
Methotrexate 
5-fluorouracil 
Gemcytabine 
Hydroxycarbamide
48
Q

Which anti-metabolite can penetrate the CNS

A

Cytosine arabinoside

49
Q

How do platinum compounds work?

A

Cross-link DNA

50
Q

Which platinum compound is the one thats typically used?

A

Carboplatin

51
Q

Which stage of the cell cycle do platinum compounds work?

A

CELL CYCLE NON-SPECIFIC

52
Q

Which cytotoxic drugs are cell cycle non-specific?

A

Alkylating agents
Platinum compounds
Anti-tumour antibiotics

53
Q

Give examples of anti-tumour antibiotics

A

Doxorubicin, epirubicin
Mitoxantrone
Actinomycin - D

54
Q

How is doxorubicin cytotoxic ?

A

Free radical formation, damages DNA directly

55
Q

Why might prednisolone be indicated for patients with neoplasms?

A

Causes apoptosis of lymphoid/ mast cells

Lymphoma (?), mast cell tumours

56
Q

Why can L-asparaginase be used as an anti-cancer tx?

A

Breaks down L-asparagine

Neoplastic lymphoid cells are dependent on an external supply of L-asparagine

Inhibits protein synthesis of neoplastic cells

57
Q

What is a benefit of using L-asparaginase ?

A

It isn’t myelosuppressive

58
Q

When might L-asparaginase be indicated?

59
Q

Where would you expect to find a transitional cell carcinoma?

60
Q

Why isn’t L-asparaginase myelosuppressive?

A

Normal body cells aren’t dependent on an external L-asparagine supply

61
Q

What might you pre-treat a patient recieving L-asparaginase with?

Why?

A

Anti-histamines

Possible anaphylactic reaction - indicated if using more than once

62
Q

How can NSAIDs be beneficial in cancer tx?

A

Anti-angiogenic
Promote apoptosis
Anti-inflammatory, analgesic
Effects on stromal cells

63
Q

When might you use NSAIDs in cancer tx?

A

TCC
Prostate carcinoma

CARCINOMAS

64
Q

How does metronomic therapy work?

A

Acts on tumour microenvironment
Anti-angiogenic
Immunomodulatory - decreases T-regs

65
Q

Why is metronomic therapy useful?

A

Useful even in drug-resistant cancers

Tumours with low MI can be susceptible e.g. HSA, TCC,

66
Q

What receptor tyrosine kinase inhibitors are indicated for mast cell tumours?

A

Masitinib and toceranib

67
Q

Why are RTK inhibitors effective against mast cells?

A

KIT mutation
- constitutive activation of KIT receptor

Inhibitors stop activation and prevent downstream signalling

68
Q

What patient factor can increase the toxicity of chemo drugs?

A

Hepatic or renal function impaired

69
Q

Give an example of a drug that is both activated and metabolised by the liver.

A

Cyclophosphamide

70
Q

Which normal tissues are susceptible to damage by cytotoxic drugs?

A

Bone marrow

GIT (crypts)

71
Q

What is the nadir?

A

The lowest point

72
Q

When would you expect the nadir of neutropenia to be?

A

About a week after a dose

73
Q

When would you expect the nadir of thrombocytopenia to be?

A

Platelet nadir - around 10 days post tx

74
Q

How can you assess myelosuppression?

A

Monitor CBC frequently

Check neutrophil nadir and before administering next dose

75
Q

When should you consider prophylactic antibiotics?

A

If very low counts <0.75 x10^9

76
Q

What should you do if a chemo patient presents as sick/febrile with a neutropenia?

A

Give IV antibiotics and fluid s

77
Q

If a patient is consistently neutropenic, what should you do?

A

Lower doses

78
Q

How could you symptomatically treat a chemo patient presenting with vomiting?

A
  • Bland diet
  • anti-emetic - Maropitant, Odansetron, Metoclopramide
  • gastroprotectant - Omeprazole, sucralfate
79
Q

How could you symptomatically treat a chemo patient presenting with diarrhoea?

A

Bland diet
Pro-kolin (probiotic)
+/- metronidazole
IVFT

Sympto tx - loperamide, sulphasalazine

80
Q

How could you symptomatically treat a chemo patient presenting with anorexia?

A

Antiemetics if nauseous

Appetite stimulants (e.g. cyproheptadine, mirtazapine)

Feeding tubes for temporary support

Analgesia if in pain

81
Q

When might hair loss be associated with chemo tx?

A

If in growth phase of hair + whiskers as they grow continuously

Can be marked in poodles, bichons, some terriers

82
Q

How can doxorubicin injury be prevented?

A

Place catheter cleanly
Firmly tape in
Flush with saline

83
Q

How can you treat doxorubicin injury?

A

Ice (keeps it local),

Dexrazotane (antidote - free radical scavenger)

84
Q

How could you treat vincristine injury?

A

Hot compresses

Hylauronidase (helps it disperse)

85
Q

What specific toxicities are associated with Doxorubicin?

A

CARDIOTOXICITY

GI (Colitis)
Mast cell degranulation
Perivascular 
Pigment changes 
Cats - nephrotoxic
86
Q

What cardiac effects are associated with doxorubicin?

A

Dysrhythmias

DCM

87
Q

What doxorubicin side effect is only seen in cats?

A

Nephrotoxicity - still can give but monitor renal function

88
Q

What specific toxicities are associated with cyclophosphamide?

A

Haemorrhagic cystitis

89
Q

Why does cyclophosphamide cause a haemorrhagic cystitis?

A

ACROLEIN is a metabolite

90
Q

How can you prevent haemorrhagic cystitis developing in patients treated with cyclophosphamide?

A 
Monitor, 
Free access to water 
Opportunity to urinate 
Avoid prolonged courses 
FUROSEMIDE
91
Q

How can you treat haemorrhagic cystitis which has developed after cyclophosphamide treatment?

A

Analgesia
Oxybutinin - antispasmodic
GAGs - to coat bladder
DMSO

92
Q

What specific toxicities are vincristine associated with?

A

Peripheral neuropathies

Ileus - abdo pain - especially in cats
Constipation

Skin sloughs if perivascular injection

93
Q

What could you give to help with some of the side effects associated with vincristine?

A

Prokinetics - metaclopramide/ ranitidine

94
Q

What side effects are associated with LOMUSTINE?

How can you monitor this?

What could you give?

A

HEPATOTOXIC

Monitor ALT

Give SAMe

95
Q

Which platinum drug gives fewer side effects?

What side effects may still be present

A

Carboplatin

Nausea via CRTZ

96
Q

What side effects are associated with RTKIs?

A

MAIN - GI diarrhoea

Weight loss 
Myelosuppression
Proteinuria 
Hypertension
Muscle cramps 
Depigmentation
97
Q

What cytotoxic drugs should you NEVER give to cats?

A

Cisplatin

5 - FU (5-fluorouracil)

98
Q

What breeds are associated with the MDR1 mutation?

A 
Herding breeds:
Collies
Shelters
Australian Shepherds 
LH Whippets
99
Q

What is the effect of the MDR1 mutation?

A

Drug excretion via kidneys or into bile

Increased toxicity of some drugs

100
Q

What cytotoxic drugs shouldn’t be given to patients with the MDR1 mutation?

Why?

A

Vincristine
Doxorubicin

Act as substrates for the pump

101
Q

How could you determine if a patient has the MDR1 mutation?

BVetMed3 POS - Principles Of Oncology (5 decks)

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