Chemotherapy Flashcards
What are treatment options for cancer?
Surgery
Radiotherapy
Chemotherapy
Targeted therapies
Immunotherapy
What are the steps of the cell cycle?
G1 (gap 1, preparation for DNA replication)
R (restriction point, point in G1 where the cell becomes committed)
S (DNA replication)
G2 (preparation for mitosis)
M (mitosis, cell divsion)
What happens during G1 (gap 1)?
Preparation for DNA replication
What is R during the cell cycle?
Restriction point, where the cell become committed
What happens during S?
DNA replication
What happens during G2?
Preparation for mitosis
What happens during M?
Mitosis, cell division
What are things that make the cell cycle go around?
Growth factors
Oncogenes
What makes the cell cycle stop?
Tumour suppresor genes
What does chemo delivery do?
Reduces the amount of cells
What happens if the interval between chemo delivery is to long?
The cells grow back
How is systematic therapy delivered?
Oral or intravenous route
Regular cycles with timing dependent on the findings from pharmacokinetics (half life, excretion)
May need to delay treatment if toxicites develop
What needs to happen to chemotherapy if toxicities develop?
It needs to be delayed
What are methods of assessing drug therapy?
CT scan
PET scan
Clinical examination
What may assessing drug activity help?
Overall survival (OS)
Progression-free survival (PFS)
Improved quality of life (QoL)
What is progression free survival?
Length of time during and after treatment of a disease that a patient lives with the disease but it does not get any worse
What is overall survival?
The length of time from either the diagnosis or the start of treatment for a disease that the patient is still alive
What does an adjuvant do?
Improve survival
What does a neoadjuvant do?
May improve survival through increasing operability
What is adjuvant treatment?
Treatment given in addition to a primary treatment
What is neoadjuvant chemotherapy?
Medicines administered before surgery for the treatment of cancer
What are some different classes of cytotoxic agents?
Alkylating agents
Anti-metabolites
Mitotic inhibitors
Antibiotics
Other
What are some sites of action for cytotoxic agents?
Anti-metabolites prevent RNA synthesis by binding to DNA
Alkylating agents cross link guanine nucleobases, directly attacking DNA
Intercalating agents wedge between bases along DNA to stop polymerase and other proteins from binding (preventing DNA transcription and DNA duplication)
Spindle poisons act on tubulin, which forms the microtubules that attach to chromosomes during mitosis
What do alkylating agents do?
Attach to free guanines on seperated DNA strands, impairing DNA replication
What does the alkyl group of an alkylating agent allow?
Covalent bonds with other molecules
What is an example of an alkylating agent?
Cisplatin
What are some mechanisms of resistance against alkylating agents?
Decreases entry or increases exit of agent in cell
Inactivation of agent in cell
Enhanced repair of DNA lesions produced by alkylation
How do antimetabolites work?
Similar structure to essential metabolites required by cell prior to cell division
Can be incorporated into new nuclear material or bind with vital enzymes
What are examples of antimetabolites?
Antagonise folic acid
Antagonis purine
What are examples of spindle poisons?
Vinca alkaloids
Taxanes
What do vinca alkaloids do?
Metaphase arrest agents, blocking microtubule formation and spindle formation
What do taxanes do?
Promote spindles and freeze cells at that stage
What are the 2 classes of antimiotic antibiotics?
Anthracyclines
Non-anathracyclines
What do antimiotic antibiotics do?
Intercalate and inhibit DNA and RNA synthesis
Bind to membranes and increase permeability of ions
Free radicals disrupt DNA chain and prevent mitosis
Where during the cell cycle do alkylating agents act?
All of the stages
Where during the cell cycle do antibiotics act?
End of G1 through to the start of G2
Where during the cell cycle do antimetabolites?
S
Where during the cell cycle do metabolic inhibitors act?
During M
What is the aim of combination therapy?
Increase efficacy
What are the principles underlying combination therapy?
Different mechanisms of action
Dissimilar toxicity profile (such as both do not act with neurotoxicity)
What does having different mechanisms of action during combination therapy allow?
Synergistic or at least additive
Reduce risk of developing resistance
What are some possible side effects of chemotherapy?
Vomiting
Nausea
Alopecia (loss of hair)
Tiredness
What does moderately emetogenic chemotherapy refer to?
Moderate incidences of nausea and vomiting
What does highly emetogenic chemotherapy refer to?
High incidents of nausea and vomiting
What is CINV?
Chemotherapy induced nausea and vomiting
What is peripheral CINV?
Where drugs act on enterochromaffin cells in the gastric glands which release serotonin which acts on vagal afferent 5-HT3 receptors
Where do the gastric glands release during peripheral CINV?
Serotonin
What does serotonin act on during peripheral CINV?
5-HT3 receptors
What is central CINV?
Drugs act on brainstem NK3 receptors and cause CINV
What are examples of hormonal drugs?
Anti-oestrogen for breast cancer
Gonadorelin analogue
Anti-adrogen for prostate cancer
What is anti-oestrogen used for?
Breast cancer
What is anti-adrogen used for?
Prostate cancer
What are some things targeted drugs act against?
Epidermal growth factor receptor (EGFR)
Vascular endothelial growth receptor (VEGR)
What receptors do T lymphocytes have?
Activation and inhibitory receptors
How does immunotherapy work?
Cancer cells hide from the immune system by binding to the self receptor PD1, but drugs can inhibit this
