18 - Chemotherapy Flashcards
How does imatinib work as a chemotherapy drug?
BCR-ABL tyrosine kinase inhibitor
What factors contribute to tumour growth?
- Growth fraction: The growth fraction is the proportion of cells in a tumor that are actively dividing at any given time. A high growth fraction means that a large number of cells are actively dividing, which can lead to rapid tumor growth. In contrast, a low growth fraction means that only a small percentage of cells are actively dividing, which can slow down tumor growth.
- Duration of cell cycle: The duration of the cell cycle refers to the time it takes for a cell to divide and create two new daughter cells. Tumor cells may have a shorter cell cycle duration than normal cells, allowing them to divide more quickly and contribute to tumor growth.
- Rate of cell loss: The rate of cell loss refers to the rate at which cells in a tumor die or are destroyed.
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?
- Molecular targeting approaches
Imatinib - Alkylating agents
Carmustine - Platinum compounds
Cisplatin and Oxalplatin - Antimetabolites
Methotrexate, 5-Fluorouracil - Spindle poisons
Taxanes (paclitaxel)
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: Cancer cells can produce enzymes that can inactivate the alkylating agents, which can reduce their ability to damage the DNA.
- Enhanced repair of DNA lesions produced by alkylation: Some cancer cells can increase their ability to repair DNA damage caused by alkylating agents. This can reduce the effectiveness of the drugs by repairing the DNA damage that the drugs are meant to cause.
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
Some cancer cells can increase their ability to repair DNA damage caused by alkylating agents. This can reduce the effectiveness of the drugs by repairing the DNA damage that the drugs are meant to cause.
Azathioprine
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: - microeconomics, money relation to help you remember.
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?
Most common
- Hair loss
- Mucositis
- Nausea and vomiting
- Diarrhoea or constipation
- Neuropathy