S7.1 Cancer Chemotherapy

Question 1

What’s is the fractional cell kill hypothesis?

Answer 1

In chemotherapy, tumour and bone marrow cells are destroyed. So chemo is given in stages, not continuously, however this can cause neutropenic sepsis (low neutrophils).

Question 2

Give some tumours with different sensitivities to chemotherapy

Answer 2

Highly sensitive - lymphomas
Modest sensitivity - breast
Low sensitivity - prostate

Question 3

Which parts of cell synthesis do chemotherapy agents act on?

Answer 3

DNA synthesis
DNA replication
DNA transcription
Mitosis

Question 4

What is the mechanism of alkylating agents?

Answer 4

Platinum compounds allow covalent bonds to form between DNA strands.
This causes the strands to break.
Now DNA replication cannot occur preventing tumour growth

Question 5

What is the broad mechanism of antimetabolites?

Answer 5

Inhibit DNA formation

Question 6

What is the action of methotrexate?

Answer 6

Methotrexate inhibits dihydrofolate reductase, which is necessary to form purines, thymine and aa, so cell is unable to form DNA.

Question 7

What is the action of 5-Fluorouracil?

Answer 7

5-FU is activated to 5-FdUMP which inhibits thymidylate synthase, thus preventing pyramidines to be incorporated in DNA.

Question 8

What is the mechanism of spindle poisons?

Answer 8

SP affect microtubule dynamics by inhibiting polymerisation (taxanes) or inhibiting microtubule assembly (vinca alkaloids).
Therefore spindle microtubules cannot depolymerize, so chromatids don’t separate during metaphase.

Question 9

How can cells become resistant to chemotherapy?

Answer 9

Decreased entry or increased exit of the agent.
Inactivation of the agent in the cell.
Enhanced repair of DNA lesions produced by alkylation.

Question 10

What is the mechanism of intercalating agents?

Answer 10

E.g Doxorubicin – prevents transcription.

Question 11

What is the action of bleomycin?

Answer 11

Bleomycin forms free radicals which cuts DNA strands

Question 12

What is the route of administration of chemotherapy?

Answer 12

IV (most common, e.g pump infusion), subcutaneous injection, PO, into a body cavity (e.g bladder).

Question 13

How does chemo cause vomiting?

Answer 13

Due to action of chemotherapy drugs on the central chemoreceptor trigger zone.

Question 14

Describe skin toxicity as a chemo ADR

Answer 14

Phlebitis of veins (inflammation).
Bleomycin can cause hyperkeratosis (thickening of outer layer) and ulcers.
Busulphan and doxorubicin can cause hyperpigmentation

Question 15

Describe mucositis as an ADR of chemo

Answer 15

Inflammation of mucous epithelia lining the GI tract esp oropharynx.
Presents as sore mouth or diarrhoea

Question 16

Describe lung toxicity as an ADR of chemo

Answer 16

Bleomycin can cause pulmonary fibrosis: Lungs become scarred and breathing becomes difficult

Question 17

What is the main ADR of chemotherapy?

Answer 17

Haematological toxicity.
Causes variable effects on degree and lineages, mainly affecting neutrophils and platelets.
The risk of sepsis associated with haematological suppression is the most common cause of mortality from the treatment.

Question 18

What causes variability in chemotherapy pharmacokinetics?

Answer 18

Abnormalities in; absorption (causes gut problems), distribution (weight loss), elimination (liver and renal dysfunction), protein binding (low albumin).

Question 19

What are some important chemo DDIs

Answer 19

Vincristine and itraconazole – more neuropathy. Capecitabine and warfarin - more bleeding.
Have caution prescribing Methotrexate and penicillin.

Question 20

What do we monitor in chemotherapy?

Answer 20

Responses of the cancer to the chemo can be monitored by radiological imaging, tumour marker blood tests, and bone marrow testing.
Drug levels should constantly be monitored and organ damage should be checked for.