Chemotherapeutic agents

Question 1

What is a chemotherapeutic agent?

Answer 1

A drug used to treat cancers by:
- causing cell death
- stopping cells from dividing

Question 2

What are the routes of administration for chemotherapeutic drugs?

Answer 2

Oral
Injection
IV infusion - often given slowly and can be irritant if leakage
Topical - less common in veterinary to prevent ingestion

Question 3

How are chemotherapeutic drugs used?

Answer 3

Used alone e.g., lymphoma

Used in conjunction with radiotherapy and/or surgery e.g., mast cell tumours

Question 4

What are cytotoxic drugs

Answer 4

‘indiscriminate’

inhibit mitosis and/or damage DNA

kill rapidly dividing cells

Question 5

What cells do cytotoxic drugs target?

Answer 5

Rapidly dividing cells

e.g., neoplastic cells
Also GI tract epithelium and bone marrow cells (body has to compensate, leads to adverse effects)

Question 6

What are some examples of commonly used cytotoxic agents for lymphoma?

Answer 6

vincristine, doxorubicin, chlorambucil, cyclophosphamide

Question 7

What new types of chemotherapeutic agents do vets use?

Answer 7

Targeted therapy against specific receptors, signalling pathways and antigens

Question 8

Give examples of targeted chemotherapeutic therapies?

Answer 8

Tyrosine kinase inhibitors for mast cell tumours in dogs -masitinib, toceranib

Monoclonal antibodies vs specific tumour antigens

Question 9

What are the limitations of cytotoxic drugs?

Answer 9

Palliative not curative

Toxicity limits dosage and dosage frequency

Question 10

What is the maximum tolerated dose of cytotoxic drugs

Answer 10

Highest dose with “acceptable” side effects

Question 11

What is metronomic chemotherapy?

Answer 11

Aims: delay or slow disease progression not kill cancer cells

Inhibits angiogenesis (development of new blood vessels - inhibits blood supply to cancer cells)

Modulates immune response to cancer cells

Question 12

What is the difference between cell cycle-specific and non-specific drugs?

Answer 12

Cell cycle-specific drugs: Kill cells in a specific phase (e.g., vincristine, vinblastine).

Cell cycle non-specific drugs: Act throughout all phases (e.g., doxorubicin, cyclophosphamide).

Question 13

What are the classes of chemotherapeutic drugs

Answer 13

alkylating agents
plant alkaloids
anti-metabolites
anti-tumour antibiotics
platinum analogs
Tyrosine kinase inhibitors

Question 14

What are alkylating agents and their clinical uses?

Answer 14

Drugs that crosslink DNA, preventing replication.

Examples:
- Chlorambucil (low-grade lymphoma, immune mediated diseases)
- cyclophosphamide (lymphoma, HAS, MC)
- lomustine (lymphoma, MCT)
- Melphalan (Myeloma)

Adverse effects:
- Myelosuppression
- GI signs
- hepatotoxicity (lomustine)
- Sterile haemorrhagic cystitis (cyclophosphamide)

Question 15

What are plant alkaloids, and how do they work?

Answer 15

Bind to tubulin and disrupt mitotic spindles.

Examples:
- Vincristine (lymphoma, leukemia, IMT)
- vinblastine (mast cell tumors).

Adverse effects:
- Myelosuppression
- peripheral neuropathy
- GI signs
- Irritant if leaks from vein

Question 16

What are anti metabolites and their clinical uses?

Answer 16

Inhibit use of cell metabolites used in growth and cell division

example:
- Cytarabine (Lymphoma with CNS involvement)

Adverse effects:
- Myelosuppression
- GI signs
- Alopecia
- Hepatotoxicity

Question 17

What are anti-tumour antibiotics and their clinical uses?

Answer 17

They inhibit topoisomerase-II, causing DNA breakage & cell death & generate free radicals.

Examples:
- Doxorubicin (lymphoma, hemangiosarcoma).
- Mitoxantrone (lymphoma, bladder transitional cell carcinoma).

Adverse effects:
- Myelosuppression.
- GI signs.
- Cumulative cardiotoxicity (dogs).
- Nephrotoxicity (cats).
- Irritation if leaks from vein
- alopecia

Question 18

What is the mode of action of platinum analogs?

Answer 18

They bind DNA, causing cross-linkage and cell death.

Example:
- Carboplatin (osteosarcoma, carcinomas).

Adverse effects:
- Myelosuppression.
- GI signs.

Question 19

How do tyrosine kinase inhibitors (TKIs) work?

Answer 19

They inhibit specific tyrosine kinase receptors, such as KIT and VEGFR, which are involved in cancer cell growth.

Examples:
- Toceranib (mast cell tumors).
- Masitinib (mast cell tumors, immune-mediated diseases).

Adverse effects:
- GI signs.
- Alopecia
- weight loss
Nephrotoxicity

Question 20

Why are TKIs not as “targeted” as expected?

Answer 20

They can still affect normal cells and cause adverse effects.

Question 21

How do vets maximize the benefits of chemotherapeutics?

Answer 21

Treat small tumors with high growth fractions

Use combinations of drugs targeting different phases of cell cycle

Repeat dosing to kill more cancer cells

Question 22

How do vets minimize harm from chemotherapeutic drugs?

Answer 22

Monitor for adverse effects.

Provide symptomatic treatment (e.g., anti-emetics).

Communicate with owners about expected side effects and quality of life

Monitor patients

Question 23

How can chemotherapeutic drugs also harm people?

Answer 23

direct exposure to drugs

metabolites of the drugs being excreted by pets