Treating Cancer Flashcards

1
Q

What are the factors contributing to tumour growth?

A

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

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2
Q

What is the fractional kill ratio?

A

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.

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3
Q

What are the main cytotoxic therapeutic groups ?

A
Antimetabolites
DNA intercalaters/ alkylators
Mitotic inhibitors (spindle poison)
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4
Q

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

A

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

5 fluorouracil-inhibits thymidylate synthase needed to make thymine.

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5
Q

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

A

They inhibit DNA strand separation.

Such as platinum compounds eg cisplatin.

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6
Q

What is the major cause of resistance to DNA intercalators?

A

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

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7
Q

What is the mechanism of action of mitotic inhibitors?

A

Inhibits polymerisation of microtubule in spindle- eg vinca alkaloids

Or….

Stimulates polymerisation and prevents depolymerisation eg taxoids.

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8
Q

What are the factors influencing pharmacokinetics in chemotherapy?

A

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.

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9
Q

What is the clinical indication for cytotoxic drugs?

A

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.
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10
Q

Which chemotherapy drugs are known to be cardiotoxic?

A

Doxorubicin+ high dose cyclophosphamide. Can cause cardiomyopathy.

Etoposide and cyclophosphomide can cause arrythmias.

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11
Q

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

A

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

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12
Q

Which drugs must you be cautious in prescribing with methotrexate?

A

Penicillins, NSAIDs.

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13
Q

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

A

St johns wort, grapefruit juice.

Also interacts with warfarin

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14
Q

Which drug must not be given with vinicristine?

A

Itraconazole (anti fungal)- causes neuropathy.

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15
Q

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

A

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

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16
Q

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

A
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.