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Y4 SA - Oncology > Oncology - medical therapies > Flashcards

Oncology - medical therapies Flashcards

1
Q

What is chemotherapy?

A

Chemotherapy is genotoxic (i.e. damaging to DNA) treatment of disease by the use of chemical substances, especially the treatment of cancer by cytotoxic and other drugs

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2
Q

Chemotherapy is the mainstay treatment for which diseases?

A

Disseminated neoplastic diseases

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3
Q

Chemotherapy can be used in combination with …?

A

Surgery
Radiotherapy

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4
Q

What are the 3 requirements of chemotherapy?

A

Standardised approaches
Multiple agents (usually)
Multiple cycles

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5
Q

How is primary chemotherapy used?

A

As the sole anti-cancer treatment in highly sensitive tumour types

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6
Q

How is adjuvant chemotherapy used?

A

Treatment is given after surgery to “mop up” microscopic residual disease
- Best to be given before severity increases to increase effectiveness
- Given for tumours when there’s a high chance of metastatic disease

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7
Q

What is neoadjuvant chemotherapy?

A

Treatment is given before surgery to shrink tumour and increase chance of successful resection

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8
Q

What is concurrent chemotherapy?

A

Treatment is given simultaneous to radiation to increase sensitivity of cancer cells to RT

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9
Q

Chemotherapy is mainly active against which cells?

A

Highly proliferating tissues
- Does not specifically target cancer cells
- Cannot tell the difference between a rapidly dividing cancer cell and a rapidly dividing normal cell

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10
Q

Cells in which part of the cell cycle are chemo resistant?

A

Cells that are not actively dividing (those in G0)

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11
Q

What is the main issue with cells in G0?

A

They act as a reservoir to repopulate the tumour

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12
Q

Which 4 parts of the cell are targeted by chemotherapy?

A

DNA synthesis
RNA synthesis
Protein synthesis
Cell cycle progression

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13
Q

What are indolent tumour?

A

Slow growing

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14
Q

How are indolent tumours affected by chemotherapy?

A

Typically resistant and are best treated with other methods (surgery if possible). Adjunctive chemotherapy can still be a part of treatment but not typically the sole therapy.

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15
Q

At which point of tumour growth is chemotherapy most likely to be affective?

A

Small number of rapidly dividing cells
- high growth factor and mitotic index
- few cells in G0

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16
Q

Describe Nowell’s hypothesis on tumour cell heterogeneity

A

Cancer is the result of genetic instability
- If a cell develops a genetic mutation this is transferred to further clones
- New clones may develop further genetic mutations that can lead to cancer
- Tumours are heterogenous. As they progress there are often ‘subclones’ that have additional mutations
- If there are sufficient cells a resistant clone is very likely
- Stem cells may also pay a role

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17
Q

List 6 factors that affect chemotherapy success

A
  1. Growth fraction and mass doubling time
  2. Tumour cell heterogeneity (evolution of resistance)
  3. Inherent tumour sensitivity
  4. Drug dosage
  5. Tumour blood supply/oxygenation
  6. Interval between treatments
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18
Q

How can drug resistance be minimised?

A
  • Treat as early as possible
  • Use standard protocols
  • Use correct doses
  • Administer agents properly
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19
Q

What causes drug resistance in lymphoma and mast cell tumours?

A

Pre-treating patients with steroids

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20
Q

What factors should be considered when choosing chemotherapy agents?

A
  • What is the indication for chemotherapy
  • What is the evidence of benefit of chemotherapy for that indication
  • Chemotherapy is often palliative (longer or shorter term)
  • Balance between QoL and treatment effect
  • Signalment (may link to pharmacogenomic issues)
  • ADME
  • Co-morbidities
  • Dosing and schedule
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21
Q

ADME stands for?

A

Administration
Distribution
Metabolism
Excretion

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22
Q

How can administration affect response and side effects of chemotherapy?

A

Dose, ability to get into blood stream if oral

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23
Q

How can distribution affect response and side effects of chemotherapy?

A

Ability of molecule to get to target site
- Size of drug, vasculature, necrosis, environment
- Blood barriers e.g. blood brain barrier
Cellular uptake / efflux pumps e.g ABCB1

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24
Q

How can metabolism affect response and side effects of chemotherapy?

A

Drug activation / deactivation e.g. CYP450, glutathione s-transferase

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25
Q

How can excretion affect response and side effects of chemotherapy?

A

Clearance – hepatobiliary system, kidney, (lung)
For kidney excreted GFR correlates with adverse effects of some drugs

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26
Q

When is single agent chemotherapy indicated?

A
  • Used for exquisitely sensitive tumours e.g. Transmissible venereal tumour (TVT)
  • When second effective agent unknown
  • Tends to select rapidly for drug resistance
  • Not capable of adequate antineoplastic activity
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27
Q

What is sequential polychemotherpay?

A

Several drugs given at different times

28
Q

What is combined polychemotherapy?

A

Several drugs given at the same

29
Q

Agents given as a part of polychemotherapy should have what characteristics?

A
  • Have proven efficacy against the tumour
  • Have different modes of action
  • Affect different stages of the cell cycle
  • Have non-overlapping dose limiting toxicities
  • Not interfere with each others actions
30
Q

Is toxicity more common in combined or sequential polychemotherapy?

A

Combined

31
Q

Chemotherapy can be administered via which routes?

A

Oral
Intravenous - Bolus (rapidly) or Infusion (slowly)
IM/SC
Intracavitary

32
Q

What factors of a pateint may pose chemotherapy dosing problems

A
  • Obese patients
  • Collies and others with known drug sensitivity
  • Animals with hepatic functional compromise
  • Animals with reduced renal function
33
Q

When using high dose chemotherapy what needs to be communicated to owners?

A
  • If we start too low treatment is ineffective
  • If we start too high it will be toxic
  • Hence need to give a dose that is safe for most patients, management any issues and adjust dose if severe AEs (typically 10% reduction is sufficient)
34
Q

At what dose should chemotherapy be started on?

A

Maximum tolerated dose
- Most dogs tolerate chemotherapy well with minimal side effects
- Don’t start low assuming they will get sick.
- Only lower as needed based on actual adverse effects

35
Q

How is the interval between chemotherapy drug doses designed?

A

To allow recovery of normal tissues
- Rapidly dividing tissue such as bone marrow and GI tract have tremendous capacity to repair rapidly
- These tissues tend to repair more rapidly than most tumours

36
Q

What happens if chemotherapy treatments are too close together or too far apart?

A

Too close = cumulative toxicity or normal tissue - so damage to normal and tumour tissue
Too far = number of cells in normal and tumour tissue doesn’t decrease overall

37
Q

CHOP chemotherapy uses which combined agents?

A

Vincristine
Doxorubicin
Cyclophosphamide
Prednisolone

38
Q

CEOP chemotherapy uses which combined agents?

A

Vincristine
Epirubicin
Cyclophosphamide
Prednisolone

39
Q

Compare first line chemotherapy protocols for lymphoma in dogs and cats

A

Dogs = CHOP or CEOP
Cats = High dose COP or chlorambucil/pred (low grade)

40
Q

How should patients be assessed before chemotherapy?

A
  • Discuss tolerance of any previous treatment
  • Assess patient
  • Assess tumour status
  • Biochemistry
  • Haematology prior to each treatment
  • Urinalysis start or treatment, prior to cyclophosphamide
41
Q

How should you plan for chemotherapy treatment?

A
  • Discuss risks and benefits for patients with owner
  • Ensure the owners context is appropriate for their pet to give chemotherapy: not pregnant or planning to be, no very young children
  • Practice set up and staffing is sufficient to administer the drugs safely
  • Appropriate PPE is available
  • Written owner info
42
Q

Describe the effects of immediate chemotherapy toxicity?

A

<24hrs
- Anaphylaxis/hypersensitivity
- Cardiac arrythmias
- Emesis

43
Q

How is anaphylaxis/hypersensitivity due to immediate chemotherapy toxicity managed?

A

IVFT, dex iv, H1 blocker, adrenaline

44
Q

How are cardiac arrythmias due to immediate chemotherapy toxicity managed?

A

Doxorubicin

45
Q

Which cancer cases are at risk of acute tumour lysis syndrome (due to chemotherapy toxicity)

A

Large tumour burdens
Rapid destruction of cancer cells e.g. lymphoma
First 24 – 48 hours

46
Q

Describe the clinical pathology and management of acute tumour lysis syndrome (due to chemotherapy toxicity)

A

Electrolyte abnormalities
Acute kidney injury
Careful monitoring of at risk patient
Early IVFT
Management of AKI

47
Q

List the main general side effects of chemotherapy

A
  • Bone marrow: lowest white count typically 7 – 10 days
  • Alopecia: uncommon in dogs /cats except a few breeds
  • GI: does not usually lasts longer than the first 4 days
  • Rapidly dividing cells most affected
  • Most side effects are transient and self resolving
  • <10 % have side effects -> hospitalisation
  • 1 – 2 % chance of death (usually sepsis)
48
Q

Describe chemotherapy toxicity 1-5 days post treatment

A
  • Direct damage to enterocytes
  • Anorexia, nausea, vomiting, diarrhoea
  • Disrupted mucosal barrier with neutropenia increases risk of sepsis (…bacterial translocation)
49
Q

Describe pre-emptive / home management of GI toxicity (1-5 days post chemotherapy treatment)

A

Maropitant – dispense for home use to prevent vomiting
Not so effective for nausea
Pre-treatment fasting reduces diarrhoea
Consider dispensing smectite in case of diarrhoea (VBS clay)
Probiotics ineffective

50
Q

GI toxicity is most severe in which cases?

A

Signs prolonged longer than 24 – 48 hours
Patient unwell / off food

51
Q

Describe chemotherapy toxicity 7-10 days post treatment

A
  • Dip in neutrophil counts for 48 – 96 hours typically
  • Too low = risk of sepsis
52
Q

Describe management of pyrexic neutropenic patients post chemotherapy

A
  • Medical emergency as may be septic
  • Translocation of bacteria from patient’s own GI flora
  • Hospitalisation - until systemically well
  • Stop all cytotoxic drugs- dose reduce next time
  • Barrier nurse and aseptic techniques
  • Supportive therapy
53
Q

Name 6 drug associated complications of chemotherapy

A
  • Cumulative cardiotoxicity (DCM)
  • Sterile haemorrhagic cystitis
  • Hepatotoxicity
  • Nephrotoxicity
  • Peripheral neuropathy
  • Fatal non-cadiogenic pulmonary oedema
54
Q

Define extravasation

A

The leakage of blood, lymph, or other fluid, such as an anticancer drug, from a blood vessel or tube into the tissue around it

55
Q

Which chemotherapy drugs are perivascular irritants?

A

Vincristine and vinblastine

56
Q

Which chemotherapy drugs are catastrophic perivascular irritants?

A

Doxorubicin, epirubicin, Actinomycin D

57
Q

How can extravasation be avoided?

A
  • ALWAYS use a cleanly placed first stick catheter
  • Monitor for any swelling, discomfort, changes in resistance to injection or rate of infusion
  • Never leave an animal unsupervised on an infusion
  • Do not use a syringe driver or pump
  • Flush catheters appropriately before catheter removal
58
Q

What should you do if you suspect extravasation?

A

If you suspect an extravasation, do not flush!
Raise vein and draw back

59
Q

How should you treat extravasation due to Doxorubicin/Epirubicin/Actinomycin D?

A

Apply COLD packs
Dexrazoxane
Topical DMSO
Consider (immediate) surgical debridement

60
Q

How should you treat extravasation due to Vincristine/Vinblastine?

A

Apply WARM compresses
Topical DMSO

61
Q

What is metronomic chemotherapy?

A

Continuous low dose chemotherapy
Usually used palliatively or after completion of MTD chemo

62
Q

Describe how metronomic chemotherapy works?

A

Main target is angiogenesis
Stimulation of immune response
Direct action on tumour cells

63
Q

What is the action of tyrosine kinase inhibitors?

A

Inhibit the activation of specific signalling pathways involved in specific types of cancer

64
Q

When are tyrosine kinase inhibitors indicated?

A

More effective in presence of KIT mutation
Licensed for incomplete excision
Generally used for metastatic disease

65
Q

What are the most common adverse affects of tyrosine kinase inhibitors?

A

Diarrhoea, vomiting and anorexia
Bone marrow suppression

Y4 SA - Oncology (12 decks)

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