Chemotherapeutics

Question 1

What is a chemotherapeutic agent?

Answer 1

A drug used to treat cancer cells by:
○ Causing cell death
○ Stopping cells from dividing

Question 2

How are chemotherapeutic drugs administered?

Answer 2

○ Oral
○ Injecting IM
○ IV infusion
Slowly into vein
Can irritate peri-vascular region
○ Topical
Can be problematic due to animals licking off and become an ingested agent

Can be used alone or as adjuvant treatment

Question 3

What types of chemotherapeutic drugs do vets use?

Answer 3

Cytotoxic drugs
Targeted therapy

Question 4

How do cytotoxic drugs work?

Answer 4

Inhibit mitosis and/or damage DNA
Very direct effect
Indiscriminate - Can affect healthy body cells not just tumour cells
Gastrointestinal tract epithelium
Can lead to diarrhoea
Bone marrow
Leads to immunosuppression

Question 5

Examples of cytotoxic drugs for treating lymphomas

Answer 5

Vincristine
Doxorubicin
Chlorambucil
Cyclophosphamide

Question 6

How does targeted therapy work?

Answer 6

Newer approach
Specifically targets:
○ Receptors
○ Signalling pathways
○ Antigens
Won’t affect body’s cells as much

Question 7

Examples of targeted therapy drugs

Answer 7

○ Tyrosine kinase inhibitors for mast cell tumours in dogs
Masitinib
Toceranib
○ Monoclonal antibodies against specific tumour antigens

Question 8

What are the limitations of cytotoxic drugs?

Answer 8

Adverse side effects due to indiscriminate effect
Gastrointestinal tract epithelium
Can lead to diarrhoea
Bone marrow
Leads to immunosuppression

Palliative not curative
Toxicity limits dose or frequency of dose

Question 9

What is the maximum tolerated dose?

Answer 9

Highest dose with ‘acceptable’ side effects
If patient can’t tolerate dose - reduce for next time

Question 10

How can we reduce the risk of toxicity with cytotoxic drugs?

Answer 10

Metronomic chemotherapy (MC)
○ Very low dose chemotherapy on a more regular basis
○ This aims to delay or slow disease progression not kill cancer cells
○ Inhibits angiogenesis - targeting blood supply to tumour
○ Modulates response to cancer cells

Question 11

How do we maximise Benefits?

Answer 11

• Earlier we start treatment the higher proportion of rapidly dividing cells that the chemotherapeutic agent can act on
  ○ Best to start treating when tumours are small
  § Plenty of rapidly dividing cells to target
  
  • Cell cycle specific drugs kill a limited number of cells with each dose
  • We need to:
    ○ Repeat dosing as often as possible
    ○ Use combinations of drugs
    § To target different phases
    § That work in different ways

Question 12

How do we minimise harm?

Answer 12

• Be aware of adverse effects
  ○ Symptomatic treatment
  § E.g. Anti-emetic drugs if nauseous
  ○ Monitor your patients
  ○ Communicate with owners
  
  • Quality of life must be maintained
    ○ How do we assess this?
    What side effects don’t we see?