18 - Chemotherapy Flashcards
How does imatinib work as a chemotherapy drug?
BCR-ABL tyrosine kinase inhibitor
What factors contribute to tumour growth?
- Short window to get in with treatments before death!
- Chemotherapy can only work on cells in the cell cycle as there is variations of 9 to 43 hours with cancer cells making it hard to target them
What is the fractional cell kill hypothesis?
A defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells so…
- Fraction of cells killed not number of cells killed
- Given in doses to allow bone marrow to recover (this recovers faster than cancer cells)
How are tumours classfied based on their chemo-sensitivity and give some examples of tumours in each category?
- High will only need chemo
- Low may not respond to chemo at all so need surgery
What are the different groups of chemotherapy drugs based on their mechanisms of action?
- Antimetabolites
- Antibiotics
- Alkylating/Platinating agents
- Mitotic spindle inhibitors
What is the mechanism of action of alkylating agents/platinating agents and what are some examples of these drugs?
- Target DNA synthesis in G1/S phase
- Forms covalent bonds with DNA nucleosides disrupting structure and preventing replication
- Stops DNA replication
What are some specific ADRs of alkylating/platinating agents?
- Peripheral, sensory and motor neuropathy
- High frequency ototoxicity
What are some possible mechanisms of resistance to alkylating agents?
- Decreased entry or increased exit of agent
- Inactivation of agent in cell
- Enhanced repair of DNA lesions produced by alkylation
What are some examples of antimetabolites and what are their mechanism of action?
- Methotrexate: in malignancy works as dihydrofolate reductase inhibitor stopping DNA synthesis
- 5-Fluorouracil: Inhibits thymidylate synthase which is needed to make pyrimidines for DNA synthesis
What are some examples of microtubule/spindle poisons and what is their mechanism of action?
- Vinca Alkaloids: Vincristine which is a microtubule assembly inhibitor
- Taxanes: Paclitaxel which is a microtubule depolymerisation inhibitor
- Cells cannot undergo prometaphase and anaphase as tubulin proteins affected. Cell cannot divide properly so cell undergoes apoptosis
What is an adverse drug reaction associated with spindle poisons?
Neurotoxicity: glove and stocking peripheral neuropathy
When is chemotherapy used and why is there different responses with the same chemotherapy on the same cancer?
CANCER: different schedules used to balance side effects and best anticipated outcome
Predicted response depends on each patients:
- performance score
- clinical score
- prognostic factors
- molecular or cytogenetic markers
What are the different routes of administration for chemotherapy?
What are the two different types of IV pump that can be used in chemotherapy?
- With Hickman it goes into SVC and patient can wear a pump of chemo
- Both methods the patient can go home
What are the common side effects of chemotherapy?