Cytotoxic Agents

Question 1

What is primary chemotherapy?

Answer 1

For advanced stages
Relieve tumour-related symptoms
Improve QoL

Question 2

What is neoadjuvant chemotherapy?

Answer 2

Before or with surgery to reduce size of primary tumour

Question 3

What is adjuvant chemotherapy?

Answer 3

After surgery/radiation to kill remaining cancer cells
Reduce incidence of local and systemic recurrence

Question 4

CHT administered depends on what?

Answer 4

Cancer type and stage
Previous and existing medical history
Whether CHT was received previously

Question 5

What does cell-cycle dependent mean?

Answer 5

Kills existing cells when not dividing

Question 6

What does cell cycle dependent mean?

Answer 6

Cell needs to be dividing to treat it

Question 7

Why do tumours need to be caught early?

Answer 7

As agents only kill a constant fraction of cells rather than a constant number

Question 8

What is the Gompertzian tumour growth curve?

Answer 8

Growth fraction decreases exponentially with time
Growth slows due to lack of resources and drug can only kill a certain fraction

Question 9

What do antimetabolites do?

Answer 9

Inhibit DNA synthesis

Question 10

What do plant derivatives do?

Answer 10

Inhibit mitosis

Question 11

What do alkylating agents do?

Answer 11

Induce DNA damage

Question 12

What do antineoplastic antibiotics do?

Answer 12

Induce DNA damage

Question 13

What is alkylation?

Answer 13

Transfer of an alkyl group from one molecule to another

Question 14

What is the mechanism of action of alkylating agents?

Answer 14

Alters double helix shape of DNA - G to T base
Depurination - DNA strand breakage
ds rxn - crosslinking DNA
mismatching of DNA bases - miscoding

Question 15

What are the mechanisms of acquired resistance?

Answer 15

Increase activity of DNA repair enzymes
Decrease transport of alkylating drug into cell
Increase activity of glutathione

Question 16

What are side effects of alkylating agents?

Answer 16

Long term damage to rapidly growing tissues
Nausea and vomiting
Systemic toxicity

Question 17

What are Platinum Analogues?

Answer 17

Alkyl like agent that kills cells in all stages of cell cycle eg. Cisplatin

Question 18

What is Cisplatin’s mechanism of action?

Answer 18

Acts as an electrophile and forms two bonds to either N7 or N3

Question 19

What do antimetabolites do?

Answer 19

Inhibit DNA or RNA synthesis eg. Fluorouracil

Question 20

What are antimetabolites mechanism of action?

Answer 20

Act as a defective version of an enzyme that is used in DNA/RNA synthesis

Question 21

What do plant derivatives do?

Answer 21

Inhibit mitosis - formation of daughter cells
Require actively replicating cells

Question 22

What is the MoA of Vinca alkaloids and taxanes?

Answer 22

Microtubule inhibitors
Mitotic arrest in metaphase - leads to cell death

Question 23

What are anti-neoplastic antibiotics?

Answer 23

DNA damaging agents eg. Anthracyclines

Question 24

What is the MoA of anti-neoplastic antibiotics?

Answer 24

Block DNA/RNA synthesis
Causes DNA strand scission
Interfere with cell replication

Question 25

What is the MoA of anthracyclines?

Answer 25

Inhibit topoisomerase II
Interchelate into DNA
Generate free radicals - target cell for apoptosis
Binds to cell membrane to alter fluidity and transport