Chemotherapy Flashcards Preview

PoD > Chemotherapy > Flashcards

Flashcards in Chemotherapy Deck (21):

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

1. Objective response: CT, PET scan, clinical examination
2. Improved: overall survival (OS), progression-free survival (PFS), improved QoL
3. Adjuvant treatment improves survival, following surgery it can mop up any escaped tumour cells
4. 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



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



Where in the cell cycle do mitotic inhibitors work?



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


Example of antibiotic in chemotherapy



Where in the cell cycle do antibiotics work in chemotherapy?

G1, S and G2



- Important in colon cancer
- Stops replication at replication fork
- Mixture of drugs such as 5FU


Aim of combination therapy

- Different drugs have different mechanisms of action and resistance
- You can catch cells at different points in the cell cycle and take advantage
- Side effects: shouldn't give two drugs with the same side effects (like neuropathy)
- You want them to by synergistic or at least additive
- Reduce risk of developing resistance
- You keep increasing the dose until you get the maximum tolerated dose


Side effects of chemo

- Vomitting
- Nausea
- Alopecia
- SoB
- Diarrhoea
- Mucositis
- Renal failure


Preventing vomiting:

- Chemo has a direct effect on the enterochromaffin cell in gut, its responsible for serotonin release
- If you give someone a serotonin antagonist, NK1 receptor antagonist and steroids then you can present vomiting in 90%