chemotherapy Flashcards
treatment options in cancer
surgery radiotherapy chemotherapy - IV/oral targeted therapies immunotherapy
frequency of chemo delivery
when there is too long an interval between courses of cytotoxic therapy, it allows increases in tumour cell population
delivery systemic therapy
oral/IV
regular cycles with timing dependent on the findings from pharmacokinetics
may be need for delay if toxicities develop
intensification depends on tumour
methods of assessing drug actvity
- objective response in advanced disease: CT/PET, clinical examination
- improves
a. overall survival
b. progression free survival
c. improved QOL - adjuvant treatment improves survival
- neoadjuvant may improve survival through increasing operability or reduced the field of radical radiotherapy
classification of cytotoxic agents
alkylating agents anti-metabolites mitotic inhibitors antibiotics others
site of action of cytotoxic agents
work at a cellular level DNA synthesis = anti-metabolites DNA = alkylating agents DNA transcription/duplication: intercalating agents mitosis: spindle poisons
mode of action of alkylating agents
○ 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
Cant act as templates for new DNA formation therefore replication is impaired
mechanism of resistance in alkylating agents
decreased entry/increased exit of agent
inactivation of agent in cell
enhanced repair of DNA lesions produced by alkylation
mechanism of action of anti-metabolites
○ Similar chemical structure to essential metabolites required by cell prior to cell division
○ May be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division
mechanism of action of vinka alkaloids
Metaphase arrest agents, bind to tubuli and block microtubule formation and spindle formation (essential for metaphase of mitosis)
mechanism of action of taxanes
Promote spindles and freeze cells at that stage of cycles
mechanism of action of antimitotic antibiotics
○ Anthracyclines and non-anthracyclines
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 cytotoxic compounds
Alylation blocking DNA replication
aim of combination therapy
balance between activity and safety
- different mechanisms of action
- different mechanisms of resistance
- compatible side effects
principles underlying combination therapy
- Combine those with:
Different mechanism of action: Synergistic or at least additive; Reduce risk of developing resistance
Dissimilar toxicity profile e.g. not both with neurotoxicity (cisplatin and taxane)
Give each to maximum tolerated dose
possible side effects of chemotherapy Myelisuppression
Alopecia Cardiotoxicity Cystitis Diarrhoea Local reaction Myalgia Myelosuppression Mucositis Nausea Neuropathy Pulmonary fibrosis Phlebitis Renal failure Sterility Vomiting
