Principles of Anti-Cancer Drug Therapy Flashcards

1
Q

What is chemotherapy?

A

The use of cytotoxic drugs to treat cancer, they tend to target rapidly dividing cells.

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2
Q

What differs in the use of chemotherapy in animals and in humans?

A

Often in animals it is less intensive and lower dose, so there are less side effects. QoL is paramount, as it is usually to prolong life and not to cure the disease.

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3
Q

What are some indications of chemotherapy?

A

Primary treatment of disseminated diseases, adjuvant therapy after surgery, following incomplete resection, neo-adjuvant therapy before surgery.

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4
Q

What type of tumours is chemotherapy likely to work better (which microscopic feature)?

A

Most drugs work best on rapidly dividing cells, with a high mitotic index, as they are most sensitive.

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5
Q

What are the 5 classes of chemotherapy drugs? Which are cell cycle specific?

A

Mitotic spindle inhibitors (cell cycle specific G2/M), Anti-metabolites (cell cycle specific S), Alkylating agents, anti-tumour antibiotics, platinum compounds.

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6
Q

How do mitotic spindle inhibitor chemotherapy drugs work? Can you think of any examples of these drugs?

A

Bind to tubulin and prevent normal assembly of microtubules, causing arrest in metaphase of M. e.g. Vincristine, vinblastine.

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7
Q

How do anti-metabolite chemotherapy drugs work? Can you think of any examples of these drugs?

A

Mimic normal substrates used in nucleic acid metabolism and interfere with DNA synthesis e.g. Cytosine, 5-fluorouracil, azothiprine.

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8
Q

How do Alkylating agent chemotherapy drugs work? Can you think of any examples of these drugs?

A

Cause cross linkage and breaking of DNA strand e.g. Cyclophosphamide, lomustine, chlorambucil.

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9
Q

How do anti-tumour antibiotic chemotherapy drugs work? Can you think of any examples of these drugs?

A

Prevent DNA/RNA synthesis e.g. Doxorubicin.

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10
Q

How do platinum compound chemotherapy drugs work? Can you think of any examples of these drugs?

A

Cause cross linkage and breakage of DNA. e.g. Cisplatin, carboplatin.

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11
Q

At what stage in tumour growth is treatment most effective? When should you start treatment?

A

LOG phase of growth, more dividing cells = more susceptible. Start ASAP. After surgery need to let wound heal first.

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12
Q

What is the cell kill hypothesis?

A

Tumour cell kill follows first order kinetics e.g. given dose doesn’t kill certain number of cells, they kill a fixed percentage.

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13
Q

How should chemotherapy drugs be dosed?

A

The maximum tolerated dose (MTD) should be given to produce highest fraction kill, but avoid adverse effects. Multiple doses given, in pulses.

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14
Q

How should the Maximum tolerated dose of chemotherapy drugs be calculated?

A

Usually correlates better to surface area so usually given in mg/m^2 - need to convert. >10kg dogs and cats may be given in mg/kg.

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15
Q

What drugs does the COP-based protocol for lymphoma contain?

A

Cyclophosphamide, Vincristine (Oncovin), Prednisolone.

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16
Q

What drugs does the LOPP protocol for treatment of T cell lymphoma contain?

A

Lomustine, Vincristine (Oncovin), Procarbizine, Prednisolone.

17
Q

What are the four stages of chemotherapy?

A

Induction, Maintenance (in some protocols), Re-induction, Rescue.

18
Q

How do multi-drug resistance (MDR1) genes help resistance to chemotherapy drugs?

A

MDR1 can be activated and cause increased P-glycoprotein expression. This pumps the drug out of the cell.

19
Q

What is metronomic chemotherapy? Which drug is most commonly used?

A

Low doses of cytotoxic drugs given on a continuous/semi-continuous basis, usually with an NSAID. Low dose cyclophosphamide commonly used.

20
Q

What are the aims of metronomic chemotherapy?

A

Slow growth by inhibiting angiogenesis and (via immunomodulatory effects) decrease circulating reg T cells and promote anti-tumour immunity.