Chemotherapy (systemic anti-cancer treatments) Flashcards
why is understanding the workings of the cell cycle important in the use of anti-cancer chemotherapy?
chemotherapy drugs are toxins at different parts of the cell cycle- they affect it in different ways and at different stages of the cycle
what are the 2 treatment effects we carry out with chemotherapy
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
how do you deliver systemic therapy?
oral or intravenous route
with regular cycles
may be need for delay if toxicities develop
RECIST criteria?
a set of published rules that define when tumors in cancer patients improve (“respond”), stay the same (“stabilize”), or worsen (“progress”) during treatment.
meaning of an adjuvant in chemotherapy terms
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
neoadjuvant chemotherapy meaning
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
different meanings of term ‘improvement’ in chemotherapy
overall survival OS
progression-free survival ie at what point does the cancer progress
improved quality of life QoL ie quality of time left
Etoposide is commonly used to treat which cancer?
lung
Alkylating agents:- chemotherapy
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
what is cisplatin? and how does it work?
cisplatin is a chemotherapy drug and is an example of an alkylating agent
how do cancer cells try to prevent alkylating agents (chemo drugs) from being effective? ie how do they build resistance
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
Antimetabolites? what do they do?
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
what is methotrexate?
a common anti-metabolite drug
Vinca alkaloids- what do they do?
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
Taxanes- what do they do?
promote spindle assembly and ‘freeze’ cells at that stage of cycle
what do you do if cells get through after using chemo drug that prevents DNA replication etc?
then use one that tries to arrest them during cell division
go for a different stage
Antimitotic antibiotics?
Anthracyclines and Non-anthracyclines.
intercalate and inhibit DNA and RNA synthesis
prevent mitosis
Spindle poisons do what?
stop cells from replicating prevent mitosis
What is the name given for the types of drugs that target DNA transcription or duplication?
intercalating agents
combination therapy
using more than one drug together
have to balance risk
may be too toxic for some patients
which types of drugs would you combine together?
those with different mechanism of action
synergistic or at least additive
or dissimilar toxicity profile ie not both with neurotoxicity
Possible side effects of chemotherapy
alopecia mucositis nausea/vomiting diarrhoea neuropathy local reaction renal failure
hormonal drugs for systemic therapy
anti-oestrogen Tamoxifen:- for breast cancer
anti-androgen for prostate cancer
these deprive the cancer of these things so reduces their growth
Targeted drugs against epidermal growth factor receptor (EGDR)
gefitinib
erlotinib- oncogene mutations in lung cancer
Targeted drugs against vascular endothelial receptor VEGF
Bevacisumab
Immunotherapy against cancer
going to be important in the future
which immunotherapies have been approved in melanoma treatment?
Combinations of Ipi and Nivo
What are the side effects of immunotherapy like?
immune-mediated eg colitis, pneumonitis, endocrinopathies (pituitary or thyroid glands stop working)
chemotherapy induced nausea and vomiting (CINV)
broadly categorised as acute (occurring within 24 hours of therapy)
delayed (persisting for 6–7 days after therapy)
anticipatory (prior to chemotherapy administration
chemotherapy- peripheral and central
can have side effects in central and peripheral nervous system ie neurological and physical actions
chemotherapy and serotonin release
emetogenic chemo- nausea causing- greater increases in serotonin release which is sent between nerve cells and causes you to feel sick
NK1 receptors and substance P
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
