Chemotherapy (systemic anti-cancer treatments)

Question 1

why is understanding the workings of the cell cycle important in the use of anti-cancer chemotherapy?

Answer 1

chemotherapy drugs are toxins at different parts of the cell cycle- they affect it in different ways and at different stages of the cycle

Question 2

what are the 2 treatment effects we carry out with chemotherapy

Answer 2

often give chemotherapy in pulses/cycles

first impact/treatment is to kill off the cancer cells
then the body needs a period of time to recover and for normal cells to try to recover
but we don’t want to let tumour cells recover too much either
then give 2nd hit of treatment but may need to go from a different angle if cancer cells that remained grew resistant

Question 3

how do you deliver systemic therapy?

Answer 3

oral or intravenous route
with regular cycles
may be need for delay if toxicities develop

Question 4

RECIST criteria?

Answer 4

a set of published rules that define when tumors in cancer patients improve (“respond”), stay the same (“stabilize”), or worsen (“progress”) during treatment.

Question 5

meaning of an adjuvant in chemotherapy terms

Answer 5

given after treatment to improve the chances of being cancer free- can’t be guaranteed though. This is why breast cancer survival rates are so much better now

Question 6

neoadjuvant chemotherapy meaning

Answer 6

given before an operation and increases the chance of having a good operation that will cure the patient. However, unfortunately only a 1/3 of people remain disease free for 5 years

Question 7

different meanings of term ‘improvement’ in chemotherapy

Answer 7

overall survival OS

progression-free survival ie at what point does the cancer progress

improved quality of life QoL ie quality of time left

Question 8

Etoposide is commonly used to treat which cancer?

Answer 8

lung

Question 9

Alkylating agents:- chemotherapy

Answer 9

they interlink DNA so that it can no longer be used as a template for DNA replication.
So cancer cells can’t replicate/grow
Stops replication at point of which it binds to DNA
affect all areas of cell cycle

Question 10

what is cisplatin? and how does it work?

Answer 10

cisplatin is a chemotherapy drug and is an example of an alkylating agent

Question 11

how do cancer cells try to prevent alkylating agents (chemo drugs) from being effective? ie how do they build resistance

Answer 11

by decreasing entry or increasing exit of an alkylating agent to the cell

by inactivating alkylating agent in the cell

by enhancing repair of DNA lesions produced by alkylation

Question 12

Antimetabolites? what do they do?

Answer 12

they try to trick the cell into using them instead as they have similar chemical structure to the essential metabolites required by a cell prior to cell division. They become mis-incorporated into the cell

only affect S phase

Question 13

what is methotrexate?

Answer 13

a common anti-metabolite drug

Question 14

Vinca alkaloids- what do they do?

Answer 14

spindle poison
they arrest the cell during metaphase by binding to tubuli and blocking mictrotubule formation and spindle formation
so mitosis can’t occur and new daughter cells can’t be made

Question 15

Taxanes- what do they do?

Answer 15

promote spindle assembly and ‘freeze’ cells at that stage of cycle

Question 16

what do you do if cells get through after using chemo drug that prevents DNA replication etc?

Answer 16

then use one that tries to arrest them during cell division

go for a different stage

Question 17

Antimitotic antibiotics?

Answer 17

Anthracyclines and Non-anthracyclines.
intercalate and inhibit DNA and RNA synthesis
prevent mitosis

Question 18

Spindle poisons do what?

Answer 18

stop cells from replicating prevent mitosis

Question 19

What is the name given for the types of drugs that target DNA transcription or duplication?

Answer 19

intercalating agents

Question 20

combination therapy

Answer 20

using more than one drug together
have to balance risk
may be too toxic for some patients

Question 21

which types of drugs would you combine together?

Answer 21

those with different mechanism of action
synergistic or at least additive
or dissimilar toxicity profile ie not both with neurotoxicity

Question 22

Possible side effects of chemotherapy

Answer 22

alopecia
mucositis
nausea/vomiting
diarrhoea 
neuropathy 
local reaction
renal failure

Question 23

hormonal drugs for systemic therapy

Answer 23

anti-oestrogen Tamoxifen:- for breast cancer
anti-androgen for prostate cancer
these deprive the cancer of these things so reduces their growth

Question 24

Targeted drugs against epidermal growth factor receptor (EGDR)

Answer 24

gefitinib

erlotinib- oncogene mutations in lung cancer

Question 25

Targeted drugs against vascular endothelial receptor VEGF

Answer 25

Bevacisumab

Question 26

Immunotherapy against cancer

Answer 26

going to be important in the future

Question 27

which immunotherapies have been approved in melanoma treatment?

Answer 27

Combinations of Ipi and Nivo

Question 28

What are the side effects of immunotherapy like?

Answer 28

immune-mediated eg colitis, pneumonitis, endocrinopathies (pituitary or thyroid glands stop working)

Question 29

chemotherapy induced nausea and vomiting (CINV)

Answer 29

broadly categorised as acute (occurring within 24 hours of therapy)
delayed (persisting for 6–7 days after therapy)
anticipatory (prior to chemotherapy administration

Question 30

chemotherapy- peripheral and central

Answer 30

can have side effects in central and peripheral nervous system ie neurological and physical actions

Question 31

chemotherapy and serotonin release

Answer 31

emetogenic chemo- nausea causing- greater increases in serotonin release which is sent between nerve cells and causes you to feel sick

Question 32

NK1 receptors and substance P

Answer 32

In the vomiting centre in the medulla there is a high conc of substance P and its receptor in addition to seratonin and their activation stimulates the vomiting reflex