Chemotherapy

Question 1

What are the objectives of chemo?

Answer 1

prolong life
minimise suffering
minimise stress/discomfort
remission
improve and maintain quality of life

Question 2

Name the different options for cancer treatment. (6)

Answer 2

surgery
radiotherapy
chemotherapy
multimodality
novel treatments
pallative care/euthanasia/do nothing

Question 3

What is the definition of chemotherapy?

Answer 3

kill/inhibit the growth of infectious agents or foreign cells (where cancer is the foreign cell)

Question 4

How would you assess whether a patient is fit for chemo? (4)

Answer 4

confirm diagnosis and stage the extent
exclude any concurrent disease
treat paraneoplastic syndromes/manage concurrent disease
assess bone marrow function

Question 5

Define “Tumour Growth Fraction”

Answer 5

The percentage of cells that are actively cycling (not in G0)
-success of chemo is highly dependent on this

Question 6

Define “mass doubling time” (MDT)

Answer 6

time taken for a tumour to double in size

Question 7

What do MDT depend on? (3)

Answer 7

growth fraction
cell cycle transit time
proportion of dying cells

Question 8

What is the ‘fraction kill hypothesis’?

Answer 8

drug kills a fixed percentage of cells rather than a fixed number. e.g. 50%
-cancer drugs should be used at as high a dose as possible to give the highest possible fraction kill

Question 9

Name the 7 groups of drugs used to treat cancer.

Answer 9

Alkylating agents
Antitumour antibiotics
Tumour antimetabollites
Platinum compounds
Plant derivatives
Miscellaneous (L-asparaginase)
Hormones

Question 10

Name the features of Alkylating agents and how they work.

Answer 10

They contain alkyl groups.
They form covalent bonds with nucleophillic molecules with in the cells; they’re main target being DNA.
They are most active in S phase although are cell cycle non specific.
They cause interstrand and intrastrand crosslinking which inhibits replication and transcription.

Question 11

What are the pharmacokinetic properties of cyclophosphamide? (6)

Answer 11

Liver metabolism is essential for it’s cytotoxicity
Drug is delivered via the bloodstream so an adequate blood supply is required.
It can cross membranes by active and passive processes.
It is activated within the cell.
Renal excretion.
Side effects include: nausea and vomiting, myelosuppresion and haemorrhagic cystitis (caused by acrotein).

Question 12

Name the mechanism of action of lomustine.

Answer 12

forms interstrand crosslinking of DNA which interferes with synthesis and function of DNA, RNA and proteins.

Question 13

What are the side effects of lomustine?

Answer 13

Myelosupprestion
Hepatotoxicity
Thrombocytopenia

Question 14

Name properties, mechanism of action and side effects of cisplatin (a platinum compound)

Answer 14

It contains 2 chloride atoms and 2 ammonia groups.
Same mechanism of action as alkylating agents: inhibits intrastrand crosslinking (IS THIS RIGHT????)
Excreted in the urine.

Side effects: nephrotoxic (give fluids and diuresis alongside it) and can cause nausea and vomiting (by damaging GIT AND triggering CTZ)

Question 15

Name the 3 groups of antitumour antibiotics

Answer 15

anthracyclines
dactinomycin
hyroxyurea

Question 16

What is the mechanism of action of anthracyclines?

Answer 16

Inhibit DNA and RNA synthesis by inter-calculating into DNA and inhibiting Topoisomerase II

Question 17

Do anthracyclines have any side effects?

Answer 17

YES.
They are cardiotoxic.
They are also nephrotoxic in cats.

Question 18

What are the pharmacokinetics of anti-mettabolites?

Answer 18

They target purines and pyrimidines.
They are cel cycle specific; acting in the S phase.
They are potent myelosuppresors.

Question 19

Name 2 plant derivatives used for chemo.

Answer 19

taxones
vinca alkaloids
ectoposiae (sp???)
campothecins

Question 20

What is the mechanism of action of vinca alkaloids?

Answer 20

binds to tubulin and inhibits the production of microtubule formation causing metaphase arrest.

Question 21

What hormones are used in chemo?

Answer 21

Glucocorticoids

Question 22

How are hormones used in chemo?

Answer 22

They prevent lymphocyte proliferation: particularly useful for leukaemia and lymphoma.
They also reduce inflammation
They can reduce oedema surrounding brain tumours; decreasing ICP

Question 23

What are the side effects of the hormones used in chemo?

Answer 23

PU
PD
Polyphagia
muscle wastage
abdomen enlargement
panting and restlessness
latrogenic hyperadrenocorticism (cushings)

Question 24

Explain how L-asparaginase can be used as a tumour treatment.

Answer 24

Asparagine is an AA builiding block for cells during replication.
Some tumours lose the ability to produce their own asparagine so require and exogenous source.
L-asaparaginase breaks down asparagine to ammonia and aspartic acid so tumours can not grow.

Question 25

How can multidrug resistance come about in chemo?

Answer 25

acquired resistance can be through the P glycoproyein (ABCB1) transport pump which removes xenobiotics actively from the cell.
Over-expression of this P glycoprotein will result in resistance to many agents.
It is encoded for by the MDR gene.

Question 26

Why would you use drug combinations during chemo?

Answer 26

To avoid drug resistance.

To combine different mechanisms of action and therefore attack different cell cycle stages.

Question 27

What must you be careful of when combining chemo drugs?

Answer 27

That their toxicities do not overlap.

That they do not interfere with each other.

Question 28

What is the CHOP method?

Answer 28

Cyclophosphamide (C)
Doxorubicin (H) - an anthracycline
Vincristine (O)
Prednisilone (P)

lasts 25 weeks, survival time is 13 months.

Question 29

What is another method apart from CHOP?

Answer 29

Cyclophosphamide (C)
Vincristine (O)
Prednisilone (P)

lasts 24 months, survival time is 8 months (WHY BOTHER?!)

Question 30

Name the general side effects of chemo.

Answer 30

Perivascular reactions:
-pain, erythema, moist desquamation and necrosis
Hypersensitivity:
-vomiting, restlessness, oedema, pruritis, dyspnoea, mouth breathing (cats)
GIT disturbances
-vomiting, diarrhoea, anorexia, colitis
Myelosuppression
-neutropenia, thrombocytopenia, anaemia (IN THAT ORDER)
Active tumour lysis syndrome
-caused by a rapid release in ions due to rapid cell kill
-increased in K and PO4, decreased in Ca
-results in uric acid production and metabolic acidosis
-causes acute renal failure, acute depression, bradycardia, vomiting, diarrhoea and shock