Chemotherapy- Systemic Anti-Cancer treatment Flashcards
What is more common in systemic anti-caner treatment?
Targeted treatments and immunotherapy
When are adjuvant treatments used?
- After surgery to reduce the occurence
- improves survival
When are neoadjuvant treatments used?
as a first step to shrink a tumour before the main treatment, which is usually surgery
How do you deliver systemic therapy?
- Orally or intravenous route
- Regular cycles with timing depending on the findings from pharmacokinetics (half life, excretion)
What type of tumours are better to deliver systemic therapy in?
non solid tumours
If toxicities develop…
- May be a need for delay delivering systemic therapy
Methods of assessing drug activity
CT scan, PET scan and/or clinical examination
How do we know if the treatment has improved the progression of cancer?
- Overall survival
- Progression-free survival
- Improved quality of life
Effects of neoadjuvant treatment?
may improve survival through increasing operability or reduce the “filed” of radical radiotherapy.
What are the modes of action of chemotherapy drugs?
- Alkyling agents
- Antimetabolites
- Vinca alkaloids
- Antimitotic antibiotics
How do alkyling agents work?
o Decreased entry or increased exit of agent
o Inactivation of agent in cell
o Enhanced repair of DNA lesions produced by alkylation
How do antimetabolites work?
o Similar chemical structure to essential metabolites required by cell prior to cell division
o May be incorporated into new nuclear material or bind irreversibly with vital enzymes to inhibit cell division
How do vinca alkaloids work?
o Metaphase arrest agents, bind to tubuli and block microtubule formation (essential for metaphase of mitosis)
o Taxanes promote spinles and “freeze” cells at that stage of cycles
How do Antimitotic antibiotics work?
o Anthracyclines and Non-anthracyclines:
o Intercalate and inhibit DNA and RNA synthesis
o Membrane binding and increase permeability to various ions
o Free radicals disrupt DNA chain and prevent mitosis
o Metal ion chelation resulting in cytotoxic compounds
o Alkyltion blocking DNA replication
Aim of combination therapy?
Increase efficacy while maintaining safety (compatible side effects) and activity.
Principles underlying combination therapy?
- Combining those with different mechanism of action:
o Synergistic or at least additive effect
o Reduces risk of developing resistance - Dissimilar toxicity profile eg not both with neurotoxicity
o Give each to their maximum tolerated dose
Possible side effects of chemotherapy
- Mucositis- people cant eat or drink
- Alopecia
- Pulmonary fibrosis
- Nausea/vomiting (but can be managed)
- Diarrhoea (but can be managed)
- Sterility (egg or semen storage)
- Neuropathy (in legs and is more problematic, nothing to reverse this)
- Myelosuppression
- Cardiotoxicity
What are other types of systemic therapy?
hormonal drugs and targeted drugs
Examples of hormonal drugs in systemic therapy?
o Anti-oestrogen Tamoxifen, aromatase inhibits for breast cancer
o Anti-androgen (CPA, flutamide) for prostate cancer
Examples of targeted drugs?
- Targeted drugs against:
o Epidermal growth factor receptor (EGFR)
o Vascular endothelial receptor (VEGF) which tries to have an effect on vessel formation
Example of targeted drug- TKI treatment.
Targeted treatment TKI (tyrosine kinase inhibitor) treatment is incredibly rapid. TKIS block chemical messengers (enzymes) called tyrosine kinases, which control how your granulocytes grow and multiply.
Side effects of immunotherapy?
immune mediated e.g. colitis, pneumonitis, endocrinopathies
Summary for Systemic therapy for cancer
- Not all chemotherapy
- Hopefully improving and being more specific
- Personalised medicine
- Immunotherapy is effective but not very affordable
- Molecular biology is key to progress
