List some cancers which are highly sensitive to chemotherapy
Small cell lung cancer
List some cancers which have low sensitivity to chemotherapy
Give 5 classes of chemotherapy based on their mechanism of action
Give an example for each
1) Alkylating agents - e.g. Cyclophosphamide
2) Antimetabolites - e.g. 6-Mercaptopurine
3) Anti-microtubule agents (spindle poisons) - vinca alkaloids/taxanes
4) Anthracyclines e.g. Doxorubicin
5) Platinum coordination complexes - e.g. cisplatin
What is the mechanism of action of the alkylating agents?
- Bind covalently to DNA molecules via their alkyl groups - causes cross-linking
- If the DNA tries to replicate, it will break - leads to apoptosis
Give 3 examples of antimetabolites
What is the mechanism of action of methotrexate when used as a chemotherapy agent?
Inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate
Therefore prevents purine synthesis, hence prevents DNA synthesis
What enzyme does 5-FU inhibit?
What are the two classes of anti-microtuble agents.
Give relevant examples
- Vinca alkaloids - vinblastine and vincristine
- Taxanes - Paclitaxel
What is the mechanism of action of the vinca alkaloids?
Prevents spindle formation
What is the MoA of the taxanes?
Prevents spindle depolymerisation
Give 2 examples of anthracyline antibiotics used in chemotherapy
What type of drug is cisplatin?
What is its mechanism of action
Enters cell and binds to guanine of DNA. Forms intra and inter strand cross-links - inhibits DNA replication and RNA synthesis.
What is the main way through which cancer cells become resistant to chemotherapy drugs?
Glycoprotein P pump - increases efflux
List some ways in which cancer cells may develop resistance to drugs, apart from increased efflux.
- Decreased entry of drug
- Inactivation within cell
- Enhance DNA repair caused by drug
Give 5 examples of ways in which chemotherapy may be administered
Give 10 ADRs of chemotherapy
3) Pulmonary fibrosis
5) Skin toxicity
10) Renal failure
How does mucositis present?
Sore mouth, ulcers, diarrhoea, GI bleed
Which cancer drug is known for causing pulmonary fibrosis?
Which cancer is it used for?
Bleomycin - testicular cancer
List some DDIs associated with specific chemotherapy drugs
All raise levels of chemo:
- Oral 5FU and warfarin, St John’s wort, grapefruit juice
- Methotrexate and NSAIDs/penicillin