Chemotherapy Flashcards
Frequency of chemotherapy delivery
Ideal time to deliver the next treatment is when the normal cells have recovered, you can catch cancer cells when they are at their lowest level
- If you give it too early you can get marrow aplasia, you can lead to sepsis
- You can give it too late then the cancer cells grow too much
Methods of delivery for systemic therapy
- Oral or IV
- Regular cycles with timing, depends on half life, toxicity and excretion
Methods of assessing drug activity
- Objective response: CT, PET scan, clinical examination
- Improved: overall survival (OS), progression-free survival (PFS), improved QoL
- Adjuvant treatment improves survival, following surgery it can mop up any escaped tumour cells
- Neoadjuvant may improve survival through increasing operability. It can sterilise the tumour so there is less chance of cells breaking off or can make surgery easier
Main cytotoxic agents
- Alkylating agents
- Anti-metabolites
- Mitotic inhibitors
- Antibiotics
- Others (CP11, in colon cancer)
Alkylating agents, site of action and mode of action
- Site of action: DNA
- Modes of action: alkyl group allows covalent bonds with other molecules
- DNA helix X-links intra and interstrand
- Attach to free guanines at N6 on separated DNA strands
- Cannot act as templates for new DNA, replication impaired
Alkylating agents, mechanisms of resistance
- Drugs pumped out of cells: decreased entry or increased exit of agent
- Inactivation of agent in cell e.g. glutahione
- Enhanced repair of DNA lesions produced by alkylayion
Example of alkylating agents
Cisplatin
Where is the cell cycle is alkylating agent?
- All the way round
Antimetabolites, site of action and modes of action
- Site of action: DNA synthesis
- Modes of action: ‘cheats’ metabolites. Similar chemical structure to metabolites require by cell prior to cell division
- Inhibit cell division
- May be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division
Antimetabolites, example
-Fluorouracil, incorporate fluoridated nucleoside in place of normal nucleoside (5FU instead of uracil in RNA)
Where in cell cycle is anti-metabolites
- S
Mitotic inhibitors, site of action and modes of action
- Spindle poisons
- Site of action: mitosis
- Modes of action: disrupt microtubules which pulls cells apart when it divides
Example of mitotic inhibitor
Vincristine
Where in the cell cycle do mitotic inhibitors work?
M
Antibiotics, mode of action
- Intercalate and inhibit DNA and RNA synthesis
- Membrane binding and increase permeability to various ions
- Free radicals disrupt DNA chain and prevent mitosis
- Metal ion chelation resulting in ctotoxic compounds
- Alkylation blocking DNA replication
