Treating Cancer

Question 1

What are the factors contributing to tumour growth?

Answer 1

Growth fraction- the number of cells that are actively dividing
Duration of cell cycle
Rate of cell loss

Question 2

What is the fractional kill ratio?

Answer 2

The amount of cells that are affected by the drug compared to the total number of cells. In chemotherapy you want this to be a greater proportion in cancer cells compared to healthy cells.

Question 3

What are the main cytotoxic therapeutic groups ?

Answer 3

Antimetabolites
DNA intercalaters/ alkylators
Mitotic inhibitors (spindle poison)

Question 4

What is the mechanism of action of antimetabolites? What are some examples of antimetabolite drugs?

Answer 4

They affect DNA synthesis. Eg.
Methotrexate-inhibits folate production needed to make thymine

5 fluorouracil-inhibits thymidylate synthase needed to make thymine.

Question 5

What is the mechanism of action of DNA intercalators and alkylators? What is a key example?

Answer 5

They inhibit DNA strand separation.

Such as platinum compounds eg cisplatin.

Question 6

What is the major cause of resistance to DNA intercalators?

Answer 6

DNA repair mechanisms,
decreased entry or increased exit of agent in target cell
Inactivation of agent in cell
Enhanced repair of DNA lesions produced by alkylation

Question 7

What is the mechanism of action of mitotic inhibitors?

Answer 7

Inhibits polymerisation of microtubule in spindle- eg vinca alkaloids

Or….

Stimulates polymerisation and prevents depolymerisation eg taxoids.

Question 8

What are the factors influencing pharmacokinetics in chemotherapy?

Answer 8

Route of administration
Abnormalities in absorption- DnV, compliance, gut problems
Abnormalities in distribution- weight loss, reduced body fat, ascites
Abnormalities in elimination- liver and renal dysfunction
Abnormalities in protein binding- low alb, other drugs.

Question 9

What is the clinical indication for cytotoxic drugs?

Answer 9

Obviously cancer… but

Predicted response is based on:
Performance score- 1-5. 5 is healthy, patients are treated between 1-3. 
Clinical stage of cancer
Prognostic factors
Molecular or cytogenetic factors.

Question 10

Which chemotherapy drugs are known to be cardiotoxic?

Answer 10

Doxorubicin+ high dose cyclophosphamide. Can cause cardiomyopathy.

Etoposide and cyclophosphomide can cause arrythmias.

Question 11

What are the range of side effects that chemotherapy drugs can cause?

Answer 11

Cardiotoxicity
Mucositis
Skin toxicity
Adverse effects due to removal of tumour eg GI perforation
Haematological toxicity eg neutropenia
Vomiting- can be acute, delayed onset or chronic
Lung toxicity-especially bleomycin can cause pulmonary fibrosis.
Alopecia- especially with doxorubicin, vinca alkaloids, cyclophosphamide

Question 12

Which drugs must you be cautious in prescribing with methotrexate?

Answer 12

Penicillins, NSAIDs.

Question 13

Which drugs can interact with capecitabine? (A 5 fluoro uracil?)

Answer 13

St johns wort, grapefruit juice.

Also interacts with warfarin

Question 14

Which drug must not be given with vinicristine?

Answer 14

Itraconazole (anti fungal)- causes neuropathy.

Question 15

What clinical monitoring is required to minimise ADR risk in chemotherapy drugs?

Answer 15

Response of cancer- imaging, biomarkers, bone marrow

Drug levels- eg methotrexate drug assays taken on serial days to ensure clearance from blood after folinic acid rescue.

Checks for organ damage- ECG, creatinine clearance

Question 16

What is the route through the clinical trial system for chemotherapy drugs from initial idea to prescribing?

Answer 16

Pre clinical studies on animal models
Phase I, II and III studies with increasing numbers of patients. 
Licensed by FDA
Approved by NICE
Prescribed in clinic.