Chemotherapy Flashcards
What are the different types of treatment available for cancer
Surgery Radiotherapy Chemotherapy Targeted therapies Immunotherapy
What types of chemotherapy are there
IV or oral for systemic delivery/absorption
How should systemtic therapy be delivered
Oral or intravenous route
Regular cycles with timing dependent on the findings from pharmacokinetics (half life, excretion)
May be need for delay if toxicities develop
Intensification previously evaluated: better in non-solid tumours
What methods can be used to access drug activtiy
Objective
Improved
Adjuvant
Neoadjuvant
Describe the objective method
It shows an objective response in advanced disease via CT scan, PET scan and/or clinical examination
RECIST criteria if radiological
Describe the improved method
Shows:
Overall survival (OS)
Progression-free survival (PFS)
Improved quality of life (QoL)
Describe the adjuvant method
Shows if treatment improves survival
Describe the neoadjuvant method
It may improve survival through increasing operability or reduce the ‘filed’ of radical radiotherapy (treatment before surgery)
Name the catergories that cytotoxic agents be classified into
Alkylating agents Anti-metabolites Mitotic inhibitors Antibiotics Others
What is the site of action for anti-metabolites
DNA synthesis
They impair replication
What is the site of action for alkylating agents
DNA
What is the site of action for intercalating agents
DNA transcription
DNA duplication
What is the site of action for spindle poisons
Mitosis
What is the mode of action for alkylating agents
The alkyl group allows covalent bonds with other molecules
DNA helix X-links intra- and interstrand
Attaches to free guanines at N6 on separated DNA strands
Can not act as templates for new DNA formation
What is the structure of antimetabolites
Similar chemical structure to essential metabolites required by cell prior to cell division
What is the mode of action for antimetabolites
They may be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division
Give examples of antimetabolites
Antagonise folic acid (methotrexate) Antagonise purine (6-mercaptopurine, 6-thioguanine)
What is the mode of action for vinca alkaloids
They bind to tubulin and block microtubule formation and spindle formation which is essential for metaphase of mitosis)
What are vinca alkaloids
They are metaphase arrest agents
What is the mode of action for taxanes
They promote spindles and ‘freeze’ cells at that stage of cycles
Name the categories of antimitotic antibiotics
Anthracyclines
Non-anthracyclines
Describe the features of antimitotic antibioditics
They 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
At what stage of the cell cycle do antibiotics work
End of G1
S
Beginning of G2
At what stage of the cell cycle do antimetabolites work
S phase
At what stage of the cell cycle do vincaalcaloids work
Beginning of M phase
At what stage of the cell cycle do mitotic inhibitors work
M phase
At what stage of the cell cycle do taxoids work
End of M
Beginning of G1
At what stage of the cell cycle do alkylating agents work
The whole cell cycle
G1, S, G2, M
What is the aim of combination therapy
To increase efficacy
What does combination therapy combine
Different mechanisms of action
Different mechanisms of resistances
What are the principles of combination chemotherapy
To combine those with:
Different mechanism of actions
Dissimilar toxicity profile e.g. not both with neurotoxicity (cisplatin and taxane)
What should the different mechanisms of action have
Synergistic or additive effect
Reduce risk of developing resistance
How should the drugs given in combination therapy be given
Both given to maximum tolerated dose
What are the possible side effects of chemotherapy (at least 5)
Alopecia Mucositis Plumonary fibrosis Cardiotoxicity Nausea/vomiting Local reaction Renal failure Diarrhoea Cystisis Sterility Myalgia Myelosupression Nueropathy Phlebitis
What were the most distressing side-effect of chemotherapy in 1983
Vomiting Nausea Alopecia Thought of coming for treatment Length of time treatment takes at the clinic Having to have an injection Shortness of breath Constantly tired Difficulty sleeping Affects family or partner
Side effects of chemotherapy can be…
Managed and/or prevented
Modern chemotherapy drugs are…
More tolerable
What other cancer systemic therapies are there
Hormonal
Targeted
Name some hormonal drugs used
Anti-oestrogen - tamoxifen, aromatase inhibitors
Gonadorelin analogue e.g. Goseralin (Zoladex)
Anti-androgen - CPA, flutamide
Name some targeted drugs used
Gefitinib/Erlotinib for EGFR
Bevacizumab (Avastin) for VEGF
Name some immunotherapy drugs
Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, Avelumab which are all PD-1 or PD-L1 inhibitors
What combination immunotherapy has been approved for melanoma
Ipilimumab
Nivolumab
What side effects can occur from immunotherapy
Immune mediated (e.g. colitis, pneumonitis, endocrinopathies)
In combination therapy what should be considered when choosing drugs
Drugs with similar side effects/toxicities should not be combined together
