Cancer Chemotherapy

Question 1

What are the four types of traditional chemotherapy agents?

Answer 1

Alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivatives.

Question 2

Describe the mechanism of alkylating agents

Answer 2

It usually hits guanine residuces, alkylation the 7th nitrogen. This makes it more acidic. The modified guanine can mispair with thymine residues creating a mutation. This DNA damage triggers cell death via apoptosis.

Question 3

Name the major groups of alkylating agents (NEAHNP)

Answer 3

Nitrogen mustards, Ethylenimines, Alkylsulphonates, Hydrazines and triazines, Nitrosoureas, Platinum based compounds.

Question 4

Name an examples of a Nitrogen Mustard and it’s mechanism

Answer 4

Eg = Cyclophosphamide.
It is activated by P450 enzymes in the liver where is it converted into aldophosphamide and it is then transported to other tissues where it forms phosphoramide (cytotoxic)

Question 5

Name an example of alkylsuphonates and its mechanism

Answer 5

Eg = Busulphan.
Has direct effect on the bone marrow depressing the formation of granulocytes and platelets (and red blood cells in high doeses) used in chronic granulocytic leukaemia

Question 6

Name an example of a nitrosoureas and its mechanism

Answer 6

Eg = lomustine.

Lipid soluble so can cross the BBB and be used against tumours of the brain and meninges

Question 7

Name an example of a platinum based compound and its mechanism

Answer 7

Eg = cisplatin.
Calcium from the cisplatin dissociates leaving the compound reactive. It causes intrastrand cross-linking which results in local denaturing of the DNA chain.

Question 8

What are the three major groups withing the antimetabolite class

Answer 8

Antifolate (methotrexate). Antipyrimidines (5-FU) and antipurines (thioguanine)

Question 9

Name an example of an antifolate and its mechanism

Answer 9

Eg = methotrexate.
Folate analogue so replaces folate in the body therefore interfering with thymidylate synthesis. It is lipid soluble so can pass the BBB.

Question 10

Name an example of an antipyrimidine and its mechanism

Answer 10

Eg = fluorouracil (5-FU).

It interferes with thymidylate synthesis and therefore inhibits DNA polymerase.

Question 11

Name an example of an antipurine and its mechanism

Answer 11

Eg, Fludarabine.

Fludarabine in its triphosphate form inhibits DNA polymerase

Question 12

Name some cytotoxic antibiotics

Answer 12

Anthracyclines, dactinomycin, bleomycin and mitomycin

Question 13

What is the mechanism of anthracyclines?

Answer 13

Binds to DNA and inhibits DNA and RNA synthesis. Also cytotoxic action mediated through effect on topoisomerase II.

Question 14

What is the mechanism of Dactinomycin?

Answer 14

Interferes with RNA polymerase and this prevents transcription. Also has an effect on topoisomerase II.

Question 15

What is the mechanism of bleomycin?

Answer 15

Degrade preformed DNA, causing chain fragmentation and release of free bases.

Question 16

What is the mechanism of mitomycin?

Answer 16

It cross-links DNA and may also degrade DNA through the generation of free radicles

Question 17

Name the plant derivatives sub groups

Answer 17

Vinca alkaloids, Taxanes, camptothecins and etoposide

Question 18

Name an example of vinca alkaloids and its mechanism

Answer 18

Vincristine. It binds to tubulin and prevents polymerisation into microtubules.

Question 19

Name an example of Taxanes and its mechanism

Answer 19

Paclitaxel and it freezes microtubules

Question 20

What is the mechanism of camptothecins

Answer 20

Binds to and inhibits topoisomerase 1

Question 21

Describe the mechanism of etoposide

Answer 21

Inhibits mitochondrial function, nucleoside transport and topoisomerase II

Question 22

Name other types of anticancer drugs

Answer 22

Hormone inhibitors, monoclonal antibodies, protein kinase inhibitors and miscellaneous agents.

Question 23

What are some of the major drawbacks of chemotherapy

Answer 23

Targets cell proliferation and not the more lethal properties of invasion and metastasis. Non specific, potential development of resistance, leaves some remaining cells and patient may not comply due to side effects.

Question 24

What is tumour lysis syndrome?

Answer 24

An acute side effect and metabolic emergancy. Occurs due to rapid cell lysis and large amount of metabolites in the blood. Results in hyperuricaemia (urine acid in blood), hyperphosphataemia, hyperkalaemia and hypocalcaemia. Can lead to acute renal failure, cardiac arrest and death.

Question 25

What are some of the bone marrow side effects?

Answer 25

Myelosupression (reduced production of cells). Only dividing cells affected. Can use human granulocyte-colony stimulating factors

Question 26

What are the gastro-intestinal side effects?

Answer 26

Nausea and vomiting (different agents vary on their emetogenic potential), loss of appetite, constipation due to reduced gastic motility (laxitives) an diarrhoea which may need IV fluid support.

Question 27

What are some mucositis side effects?

Answer 27

Ulceration, dry mouth, pain, taste alterations.

Question 28

What are some other general side effects of chemotherapy

Answer 28

Fatigue, body image side effects, peripheral neuropathy, altered renal function and delayed effects (infertility or secondary malignancy)