12. Cancer Chemotherapy Flashcards
When can we detect tumours?
- when there are 10^9 cells = 1 cm tumour
-when get to 10^12 patient may be dead
Want to intervene between these 2 points but ideally detect it before
Do chemo/radiotherapy work in Go?
No, which is why we may need to give drugs to push the cancer cells out of this dormant G0 phase and into the active cell cycle.
What is the fractional cell kill hypothesis?
- give pulses of chemotherapy not given continuously
- this gives bone marrow a chance to recover
- bone marrow recovers quicker than the cancer cells
Why do we classify tumours according to their sensitivity?
- highly sensitive cancers mean patients may only need chemo
- low sensitivity means chemo may be an adjunct to other treatments e.g. surgical resection and something to shrink the tumours and mop up and cells left behind
Name 3 classes of chemotherapeutic agents
1) alkylating agents e.g. platinum, DACH
2) antimetabolities e.g. methotrexate
3) spindle poisons e.g. vinca alkaloids or taxoids
How do alkylating agents e.g. platinum work?
- alkylating agents make a bond between the 2 strands of DNA locking them together
- they cant then replicate properly (cant form fork) and can get single strand break that becomes ds break and then apoptosis
- sometimes can be repaired so chemo may not work - can give biological therapies to help with repair
How do antimetabolites e.g. methotrexate and 5 fluoro uracil work?
Methotrexate: Targets dihydrofolate reductase which is necessary for purine incorporation so without it will have problems with DNA synthesis
5 fluorouracil: targets thymidylate synthase which is necessary for pyrimidine incorporation so without it will have problems with DNA synthesis
How do spindle poisons e.g. Vinca alkaloids and toxoids workwork?
Vinca alkaloids: prevent spindle formation by inhibiting polymerisation. Used in lung cancer.
Taxoids: promote assembly and prevent disassembly of microtubles.
What are the 3 main ways that a cell can develop resistance to chemotherapeutic agents?
1) decreased entry/increased exit of agent - pump on cell
2) inactivation of agent in the cell - proteins present in the cytoplasm including glutathione which can bind with agent and mop it up
3) enhanced repair of DNA lesions produced by alkylation: body’s repair mechanisms can resolve the damage
What is meant by ‘performance score’?
Scale of 1 -5
1: well enough to work, 5 is dead
Offer treatment to 1 and 2, beyond this poor prognosis and treatment might be too tough and can kill the patient
What routes of administration are there for chemotherapy?
Mainly given IV through PICC or Hickman line if over a few hours. dont really give IM.
But can pretty much give PO, subcutaneous, intrathecal, intralesional, topical and into a body cavity
What are the main side effects of chemotherapy?
- hyperuricaemia - rapid tumour lysis release urate crystals
- GI perforation at the site of tumour (lymphoma)
- DIC (AML)
- vomiting
- alopecia: hair thins 2-3 weeks
- skin toxicity
- mucositis
- cardio toxicity
- lung toxicity
What are the patterns of emesis we see in chemotherapy?
3 patterns:
Acute - within 4 -12 hrs
Delayed - 2-5 days later
Chronic - may persist over 14 days
Can also get anticipatory emesis
What might we see with skin toxicity?
- beaus lines
- extravasation
- Hyperpigmentation
- thrombophlebitis
What is mucositis?
- epithelial tract damage
- most commonly worst in oropharynx
- presents as a sore mouth/throat, diarrhoea and GI bleeds
- mouth hygiene important to prevent thrush
