Introduction to Chemotherapeutics

Question 1

What is a chemotherapeutic agent?

Answer 1

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

Question 2

What routes of administration of chemotherapeutic agents can be used?

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 are the newer chemotherapeutic agents used?

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?

Answer 10

highest dose with ‘acceptable’ side effects

Question 11

What is the aim of 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

Which cytotoxic drugs are cell cycle non-specific?

Answer 12

doxorubicin
cyclophosphamide
lomustine
chlorambucil

Question 13

Which cytotoxic drugs are cell cycle specific?

Answer 13

vincristine
vinblastine
cytarabine

Question 14

What are the classes of chemotherapeutic drugs?

Answer 14

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

Question 15

What is the mode of action of alkylating agents?

Answer 15

Alkyl group binds to and cross links DNA

Question 16

Give examples of alkylating agents

Answer 16

chlorambucil
cyclophosphamide
lomustine
melphalan

Question 17

What is the clinical use of alkylating agent - chlorambucil

Answer 17

low grade lymphoma (cats)
immune mediated diseases

Question 18

What is the clinical use of alkylating agent - cyclophosphamide?

Answer 18

lymphoma
haemangiosarcoma
metronomic chemotherapy

Question 19

What is the clinical use of alkylating agent - lomustine?

Answer 19

lymphoma
mast cell tumour

Question 20

What is the clinical use of alkylating agent - melphalan?

Answer 20

myeloma

Question 21

What are the adverse effects of alkylating agents?

Answer 21

Myelosuppression
GI signs
Sterile haemorrhagic cystitis (cyclophosphamide)
Hepatotoxicity (lomustine)

Question 22

What is the mode of action of plant alkaloids?

Answer 22

bind to tubulin cells and disrupt mitotic spindle

Question 23

Give examples of plant alkaloids

Answer 23

Vincristine
Vinblastine

Question 24

What is the clinical use of plant alkaloid - vincristine?

Answer 24

Lymphoma, leukaemia

Question 25

What is the clinical use of plant alkaloid - vinblastine?

Answer 25

mast cell tumour

Question 26

What are the adverse effects of plant alkaloids?

Answer 26

GI signs Myelosuppression Irritant if leaks from vein Peripheral neuropathy

Question 27

What is the mode of action of anti metabolites?

Answer 27

Inhibit use of cell metabolites used in growth and cell division

Question 28

Give an example of an anti metabolite

Answer 28

Cytarabine

Question 29

What is the clinical use of the anti metabolite cytrabine?

Answer 29

Lymphoma with CNS involvement

Question 30

What are the adverse effects of anti metabolites?

Answer 30

Myelosuppression GI signs Alopecia Hepatotoxicity

Question 31

What is the mode of action of anti-tumour antibiotics?

Answer 31

Inhibit topoisomerase-II causing breakage of DNA and cell death; forms free radicals

Question 32

What are examples of anti-tumour antibiotics?

Answer 32

Doxorubicin Mitoxantrone

Question 33

What is the clinical use of anti-tumour antibiotic - doxorubicin?

Answer 33

lymphoma haemangiosarcoma

Question 34

What is the clinical use of anti-tumour antibiotic - mitoxantrone?

Answer 34

lymphoma haemangiosarcoma

Question 35

What are the adverse effects of anti-tumour antibiotics?

Answer 35

Myelosuppression GI signs Extreme irritation if leaks from vein Alopecia Cumulative cardiotoxicity (dogs) Nephrotoxic (cats)<

Question 36

What is the mode of action of platinum analogs?

Answer 36

Bind platinum to DNA causing cross linkage and cell death

Question 37

What is an example of a platinum analog?

Answer 37

carboplatin

Question 38

What is the clinical use of the platinum analog carboplatin?

Answer 38

osteosarcoma carcinomas

Question 39

What are the adverse effects of platinum analogs?

Answer 39

Myelosuppression GI signs

Question 40

What is the mode of action of tyrosine kinase inhibitors?

Answer 40

Inhibit various TK receptors

Question 41

What are examples of tyrosine kinase inhibitors?

Answer 41

Toceranib Masitinib

Question 42

What is the clinical use of the TK inhibitor - toceranib?

Answer 42

mast cell tumour

Question 43

What is the clinical use of the TK inhibitor - masitinib?

Answer 43

mast cell tumour immune mediated diseases

Question 44

What are the adverse effects of TK inhibitors?

Answer 44

Weight loss GI signs Alopecia Nephrotoxicity

Question 45

How can the benefit of chemotherapeutic drugs be maximised?

Answer 45

treat small tumours with a high growth fraction - plenty of rapidly dividing cells to target Cell cycle specific drugs kill a limited number of cell each dose - repeat doses as often as possible and use combinations of drugs to target different phases in different ways

Question 46

How can the harm of chemotherapeutic drugs be minimised?

Answer 46

Be aware of adverse effects - symptomatic treatments, monitor patient, communicate with owner Ensure quality of life is maintained

Question 47

How can chemotherapeutic drugs cause harm to humans?

Answer 47

direct exposure metabolites excreted by pets