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

Principles Of Anti-cancer Drug Therapy Flashcards

(101 cards)

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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
What is the rescue phase?
Switch to different drugs if the current protocol is not effective
26
What is metronomic chemotherapy?
NSAID plus low dose alkylating agent (cyclophosphamide or chlorambucil)
27
What are RTKIs?
Receptor Tyrosine Kinase inhibitors Interfere with aberrant cell-signalling in cancer cells
28
What factors affect the success of chemotherapy?
Tumour cell type Drug distribution Development of resistance
29
How can tumour cell type affect success of chemotherapy?
Some have intrinsic resistance e.g. many carcinomas, malignant melanoma
30
How can drug distribution be compromised?
Blood supply to neoplasm Barriers to diffusion e.g. BBB
31
How can tumours develop resistance?
Tumours are genetically unstable Drug exposure selects for resistant cells
32
Describe a mechanism for drug resistance.
Multi-drug resistance pump - MDR1 gene Can be upregulated resulting in Doxorubicin and vincristine being pumped OUT
33
What shouldn’t be used to pre-treat lymphomas before chemo? Why?
Pred Glucocorticoids can cause MDR1 upregulation
34
How are alkylating agents cytotoxic?
Cross-link DNA and cause strand breakage Interfere with DNA replication and transcription
35
When in the cell cycle do alkylating agents act?
ALL THE TIME
36
Which cytotoxic drugs are alkylating agents?
Cyclophosphamide Chlorambucil Lomustine Melphalan
37
What alkylating agents are indicated for lymphoma?
Cyclophosphamide Chlorambucil Lomustine
38
Which alkylating agent is indicated for sarcomas?
Cyclophosphamide
39
What is Melphalan indicated for?
Myeloma
40
Which alkylating agent is indicated for brain tumours?
Lomustine
41
How are mitotic spindle inhibitors cytotoxic?
Binds to tubulin, interferes with mitotic spindle formation | METAPHASE ARREST
42
At what phase of the cell cycle do mitotic spindle inhibitors act?
G2/M
43
Give examples of mitotic spindle inhibitors.
Vincristine Vinblastine Vinorelbine
44
When is vinblastine indicated?
high grade MCT
45
What are anti-metabolites?
Mimic normal substrates in DNA / RNA synthesis | - inhibit enzymes or make metabolites non-functional
46
What phase of the cell cycle do anti-metabolites affect?
S phase
47
Give examples of anti-metabolites
``` Cytosine arabinoside Methotrexate 5-fluorouracil Gemcytabine Hydroxycarbamide ```
48
Which anti-metabolite can penetrate the CNS
Cytosine arabinoside
49
How do platinum compounds work?
Cross-link DNA
50
Which platinum compound is the one thats typically used?
Carboplatin
51
Which stage of the cell cycle do platinum compounds work?
CELL CYCLE NON-SPECIFIC
52
Which cytotoxic drugs are cell cycle non-specific?
Alkylating agents Platinum compounds Anti-tumour antibiotics
53
Give examples of anti-tumour antibiotics
Doxorubicin, epirubicin Mitoxantrone Actinomycin - D
54
How is doxorubicin cytotoxic ?
Free radical formation, damages DNA directly
55
Why might prednisolone be indicated for patients with neoplasms?
Causes apoptosis of lymphoid/ mast cells Lymphoma (?), mast cell tumours
56
Why can L-asparaginase be used as an anti-cancer tx?
Breaks down L-asparagine Neoplastic lymphoid cells are dependent on an external supply of L-asparagine Inhibits protein synthesis of neoplastic cells
57
What is a benefit of using L-asparaginase ?
It isn’t myelosuppressive
58
When might L-asparaginase be indicated?
Lymphoma
59
Where would you expect to find a transitional cell carcinoma?
Bladder
60
Why isn’t L-asparaginase myelosuppressive?
Normal body cells aren’t dependent on an external L-asparagine supply
61
What might you pre-treat a patient recieving L-asparaginase with? Why?
Anti-histamines Possible anaphylactic reaction - indicated if using more than once
62
How can NSAIDs be beneficial in cancer tx?
Anti-angiogenic Promote apoptosis Anti-inflammatory, analgesic Effects on stromal cells
63
When might you use NSAIDs in cancer tx?
TCC Prostate carcinoma CARCINOMAS
64
How does metronomic therapy work?
Acts on tumour microenvironment Anti-angiogenic Immunomodulatory - decreases T-regs
65
Why is metronomic therapy useful?
Useful even in drug-resistant cancers | Tumours with low MI can be susceptible e.g. HSA, TCC,
66
What receptor tyrosine kinase inhibitors are indicated for mast cell tumours?
Masitinib and toceranib
67
Why are RTK inhibitors effective against mast cells?
KIT mutation - constitutive activation of KIT receptor Inhibitors stop activation and prevent downstream signalling
68
What patient factor can increase the toxicity of chemo drugs?
Hepatic or renal function impaired
69
Give an example of a drug that is both activated and metabolised by the liver.
Cyclophosphamide
70
Which normal tissues are susceptible to damage by cytotoxic drugs?
Bone marrow GIT (crypts)
71
What is the nadir?
The lowest point
72
When would you expect the nadir of neutropenia to be?
About a week after a dose
73
When would you expect the nadir of thrombocytopenia to be?
Platelet nadir - around 10 days post tx
74
How can you assess myelosuppression?
Monitor CBC frequently Check neutrophil nadir and before administering next dose
75
When should you consider prophylactic antibiotics?
If very low counts <0.75 x10^9
76
What should you do if a chemo patient presents as sick/febrile with a neutropenia?
Give IV antibiotics and fluid s
77
If a patient is consistently neutropenic, what should you do?
Lower doses
78
How could you symptomatically treat a chemo patient presenting with vomiting?
- Bland diet - anti-emetic - Maropitant, Odansetron, Metoclopramide - gastroprotectant - Omeprazole, sucralfate
79
How could you symptomatically treat a chemo patient presenting with diarrhoea?
Bland diet Pro-kolin (probiotic) +/- metronidazole IVFT Sympto tx - loperamide, sulphasalazine
80
How could you symptomatically treat a chemo patient presenting with anorexia?
Antiemetics if nauseous Appetite stimulants (e.g. cyproheptadine, mirtazapine) Feeding tubes for temporary support Analgesia if in pain
81
When might hair loss be associated with chemo tx?
If in growth phase of hair + whiskers as they grow continuously Can be marked in poodles, bichons, some terriers
82
How can doxorubicin injury be prevented?
Place catheter cleanly Firmly tape in Flush with saline
83
How can you treat doxorubicin injury?
Ice (keeps it local), | Dexrazotane (antidote - free radical scavenger)
84
How could you treat vincristine injury?
Hot compresses | Hylauronidase (helps it disperse)
85
What specific toxicities are associated with Doxorubicin?
CARDIOTOXICITY ``` GI (Colitis) Mast cell degranulation Perivascular Pigment changes Cats - nephrotoxic ```
86
What cardiac effects are associated with doxorubicin?
Dysrhythmias DCM
87
What doxorubicin side effect is only seen in cats?
Nephrotoxicity - still can give but monitor renal function
88
What specific toxicities are associated with cyclophosphamide?
Haemorrhagic cystitis
89
Why does cyclophosphamide cause a haemorrhagic cystitis?
ACROLEIN is a metabolite
90
How can you prevent haemorrhagic cystitis developing in patients treated with cyclophosphamide?
``` Monitor, Free access to water Opportunity to urinate Avoid prolonged courses FUROSEMIDE ```
91
How can you treat haemorrhagic cystitis which has developed after cyclophosphamide treatment?
Analgesia Oxybutinin - antispasmodic GAGs - to coat bladder DMSO
92
What specific toxicities are vincristine associated with?
Peripheral neuropathies Ileus - abdo pain - especially in cats Constipation Skin sloughs if perivascular injection
93
What could you give to help with some of the side effects associated with vincristine?
Prokinetics - metaclopramide/ ranitidine
94
What side effects are associated with LOMUSTINE? How can you monitor this? What could you give?
HEPATOTOXIC Monitor ALT Give SAMe
95
Which platinum drug gives fewer side effects? What side effects may still be present
Carboplatin Nausea via CRTZ
96
What side effects are associated with RTKIs?
MAIN - GI diarrhoea ``` Weight loss Myelosuppression Proteinuria Hypertension Muscle cramps Depigmentation ```
97
What cytotoxic drugs should you NEVER give to cats?
Cisplatin | 5 - FU (5-fluorouracil)
98
What breeds are associated with the MDR1 mutation?
``` Herding breeds: Collies Shelters Australian Shepherds LH Whippets ```
99
What is the effect of the MDR1 mutation?
Drug excretion via kidneys or into bile Increased toxicity of some drugs
100
What cytotoxic drugs shouldn’t be given to patients with the MDR1 mutation? Why?
Vincristine Doxorubicin Act as substrates for the pump
101
How could you determine if a patient has the MDR1 mutation?
PCR test

BVetMed3 POS - Principles Of Oncology (5 decks)

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