Chemotherapy

Question 1

Explain why cancer kills people so soon after detection. (2)

Answer 1

The difference between detectable cancer and cancer that will kill you is only three orders of magnitudes in terms of cell number.

Question 2

Explain the type of drug commonly given with chemotherapy / radiotherapy. (3)

Answer 2

Chemo and radiotherapy only work if the cell is replicating (ie not in stage G0), so drugs are commonly given to keep cells in the replicatory phase.

Question 3

Describe the fractional kill hypothesis. (2)

Answer 3

The next dose of chemo needs to be times when the bone marrow has had enough time to recover, but the cancer has not.

Question 4

Name one example of a cancer that is highly sensitive, moderately sensitive and not sensitive to chemotherapy. (3)

Answer 4

High - lymphomas
Moderate - lung
Low - prostate

Question 5

Describe the clinical indications for chemotherapy. (2)

Answer 5

Cancer, but also other inflammatory conditions eg RA.

Question 6

Describe how the predicted response to chemotherapy is worked out. (4)

Answer 6

Depends on malignancy type, clinical stage, cytogenetic markers, performance score (4= bedbound, 0= active).

Question 7

Describe the MoA of antimetabolites. (3)

Answer 7

Interfere with DNA synthesis by inhibiting synthesis of bases by changing folate metabolism.

Question 8

Describe the MoA of alkylating agents. (3)

Answer 8

Interfere with the DNA within the cell by forming inter-strand bonds and attaching bulky side groups to mess up future replications.

Question 9

Describe the MoA of spindle poisons. (3)

Answer 9

Interfering with mitosis by inhibiting spindle polymerisation or preventing depolymerisation.

Question 10

Describe the MoA of intercalating agents. (2)

Answer 10

Interfere with DNA transcription or DNA replication.

Question 11

Describe the mechanisms of resistance to alkylating agents. (3)

Answer 11

Decreased entry of increased exit of the agent.
Inactivation of the agent within the cell (eg by glutathione)
Enhanced repair of DNA lesions.

Question 12

Describe the methods of administration of chemotherapy. Explain the indications for each. (7)

Answer 12

IV - most common - bolus, bag, pump 
PO - only if bioavailability is high
SC - convenient in community 
Body cavity - pleural, bladder
Intralesional - directly into cancer
Intrathecal - into CSF
Topical - onto skin.

Question 13

Describe the renal side effects of chemotherapy. (3)

Answer 13

Acute renal failure - hyperuricamia cause by rapid tumour cell lysis leading to urate precipitation in renal tubules.

Question 14

Describe the GI complications of chemotherapy for GI cancer. (3)

Answer 14

Perforation and peritonitis - all the tumour cells get listed and there is a hole.

Question 15

Describe the commonest cause of chemotherapy-induced DIC. (1)

Answer 15

Acute myeloid leukaemia.

Question 16

Describe the causes of vomiting induced by chemo. Describe the types. (4)

Answer 16

Direct CTZ trigger.

Acute (4-12h), delayed (2-5 days), or chronic (up to 12 days)

Question 17

Describe the common skin toxicity reactions to chemotherapy. (4)

Answer 17

Local - irritation and thrombophlebitis of veins, extravasation.
General - hyperkeratosis, hyperpigmentation, ulcerated pressure sores.

Question 18

Explain why chemotherapy induced skin toxicity effects are often severe before they present. (2)

Answer 18

Over-compliance - people put up with the skin effects because they’re worried the chemo would have to be stopped.

Question 19

Describe the common mucosal effects of chemotherapy. (3)

Answer 19

Mucusitis causing sore mouth / throat, diarrhoea, and bleeds.

Question 20

Describe the common cardiac effects of chemotherapy. (2)

Answer 20

Cardiomyopathy and arrhythmias

Question 21

Describe the common respiratory effects of chemotherapy. (1)

Answer 21

Severe pulmonary fibrosis.

Question 22

Describe the common haematological toxicity. (3)

Answer 22

Neutropenia is most common, but can be any; neutropenia can lead to sepsis.

Question 23

Describe the events that would cause absorption anomalies for chemotherapy. (3)

Answer 23

N+V
Gut problems
Low compliance

Question 24

Describe the events that would cause distribution abnormalities for chemotherapy. (3)

Answer 24

Weight loss
Reduced body fat
Ascites

Question 25

Describe the things that would cause elimination abnormalities for chemo. (2)

Answer 25

Liver or renal dysfunction

DDIs.

Question 26

Describe the things that would cause abnormalities in protein binding of chemotherapy. (2)

Answer 26

DDIs

Low albumin.

Question 27

Describe 3 important drugs that have DDIs with chemotherapy. (6)

Answer 27

Antifungals - neuropathy.
Capecitabine (anti-metabolite) - Warfarin, St Johns Wort, grapefruit juice.
Methotrexate - penicillin and NSAIDs.

Question 28

Describe how the monitoring of drugs occurs in chemotherapy. (6)

Answer 28

Response of cancer - tumour markers and radiology
Drug levels - serial assays to ensure clearance
Checks for organ damage - echo, creatinine clearance.