Chemotherapy

Question 1

List some cancers which are highly sensitive to chemotherapy

Answer 1

Lymphomas
Small cell lung cancer
Neuroblastoma

Question 2

List some cancers which have low sensitivity to chemotherapy

Answer 2

Prostate
Renal
Endometrial

Question 3

Give 5 classes of chemotherapy based on their mechanism of action
Give an example for each

Answer 3

1) Alkylating agents - e.g. Cyclophosphamide
2) Antimetabolites - e.g. 6-Mercaptopurine
3) Anti-microtubule agents (spindle poisons) - vinca alkaloids/taxanes
4) Anthracyclines e.g. Doxorubicin
5) Platinum coordination complexes - e.g. cisplatin

Question 4

What is the mechanism of action of the alkylating agents?

Answer 4

• Bind covalently to DNA molecules via their alkyl groups - causes cross-linking
• If the DNA tries to replicate, it will break - leads to apoptosis

Question 5

Give 3 examples of antimetabolites

Answer 5

• 6-Mercaptopurine
• 5-Fluorouracil
• Methotrexate

Question 6

What is the mechanism of action of methotrexate when used as a chemotherapy agent?

Answer 6

Inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate
Therefore prevents purine synthesis, hence prevents DNA synthesis

Question 7

What enzyme does 5-FU inhibit?

Answer 7

Thymidylate synthase

Question 8

What are the two classes of anti-microtuble agents.

Give relevant examples

Answer 8

• Vinca alkaloids - vinblastine and vincristine

- Taxanes - Paclitaxel

Question 9

What is the mechanism of action of the vinca alkaloids?

Answer 9

Prevents spindle formation

Question 10

What is the MoA of the taxanes?

Answer 10

Prevents spindle depolymerisation

Question 11

Give 2 examples of anthracyline antibiotics used in chemotherapy

Answer 11

Doxorubicin

Daunorubicin

Question 12

What type of drug is cisplatin?

What is its mechanism of action

Answer 12

Platinum agent
Enters cell and binds to guanine of DNA. Forms intra and inter strand cross-links - inhibits DNA replication and RNA synthesis.

Question 13

What is the main way through which cancer cells become resistant to chemotherapy drugs?

Answer 13

Glycoprotein P pump - increases efflux

Question 14

List some ways in which cancer cells may develop resistance to drugs, apart from increased efflux.

Answer 14

• Decreased entry of drug
• Inactivation within cell
• Enhance DNA repair caused by drug

Question 15

Give 5 examples of ways in which chemotherapy may be administered

Answer 15

1) IV
2) Oral
3) Intralesional
4) Intrathecal
5) Topical

Question 16

Give 10 ADRs of chemotherapy

Answer 16

1) Alopecia
2) Mucositis
3) Pulmonary fibrosis
4) N/V
5) Skin toxicity
6) Diarrhoea
7) Neuropathy
8) Myelosuppression
9) Infertility
10) Renal failure

Question 17

How does mucositis present?

Answer 17

Sore mouth, ulcers, diarrhoea, GI bleed

Question 18

Which cancer drug is known for causing pulmonary fibrosis?

Which cancer is it used for?

Answer 18

Bleomycin - testicular cancer

Question 19

List some DDIs associated with specific chemotherapy drugs

Answer 19

All raise levels of chemo:

• Oral 5FU and warfarin, St John’s wort, grapefruit juice
• Methotrexate and NSAIDs/penicillin