Session 10: Cancer Chemotherapy Flashcards
What is imatinib used for?
Chronic myeloid leukaemia
It is a Bcr-Abl tyrosine kinase inhibitor.
Explain when chemo works in the cell cycle.
Chemo only works if the cell is in the cycle, and not in G0!.
Explain the fractional cell kill hypothesis.
You give chemotherapy in cycles. The timing of administration is tailored to the recovery of the cells of the bone marrow.
Tumour cells will not recover as fast as the bone marrow does. This means that there is minimal suppression of bone marrow but still a gradual decrease of tumour growth/cell number.
Give examples of chemotherapies.
Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons
Platinum compounds
Explain the mechanism of action of platinum compounds.
There is formation of platinated inter- and intrastrand adducts.
An example is an oxaliplatin adduct which will lead to the inhibition of DNA synthesis.
Give examples of antimetabolites.
5-fluorouracil
Methotrexate
Explain the action of methotrexate.
Inhibits dihydrofolate reductase which inhibits the conversion of dihydrofolate to its active form tetrahydrofolate.
This leads to impairment of DNA synthesis.
Explain the action of 5-fluoruracil.
5-fluorouracil inhibits thymidylate synthase (TS) which converts dUMP into dTMP.
This inhibits the synthesis of DNA.
Give examples of spindle poisons.
Taxoids/Taxanes
Vinca alkaloids
Explain the mechanism of action of taxoids/taxanes.
Promotes the assembly (polymerisation) of microtubules (which are supposed to pull sister chromatids apart).
Also prevents the disassembly (depolymerisation) of microtubules.
This leads to too much formation of microtubules and the cell becoming too rigid to divide.
This means it inhibits mitosis.
Explain the mechanisms of resistance of alkylating agents.
A pump will recognise the alkylating agent and pump out the alkylating agent in order to decrease the entry/increase exit of the alkylating agent.
There can also be inactivation of the agent by glutathione inside the cell.
There can also be enhanced repair of DNA lesions that are produced by the alkylation.
Explain the mechanism of action of alkylating agents.
There is a cross linkage between the DNA strands.
This leads to DNA replication not being possible.
The predicted response is different within the same cancer (not only between different).
What is the predicted response based on?
Performance score
Clinical stage of cancer
Prognositc factors or score
Molecular or cytogenetic markers
Ways to administer chemo
IV
PO
SC
Into a body cavity such as bladder
Intralesional
Intrathecal
Topic
IM
Give examples of IV pumps.
PICC line
Hickman line
Give common side effects of chemotherapy.
Alopecia
Mucositis
Nausea/Vomiting
Diarrhoea
Cystitis
Sterility
Cardiotoxicity
Myelosuppression
Pulmonary fibrosis
Neuropathy
Myalgia
Thrombophlebitis
Give chemotherapy ADRs due to effect of treatment on the tumour.
Rapid tumour lysis leading to hyperuricaemia.
This causes precipitation of urate crystals in the renal tubules.
This leads to acute renal failure
GI perforation can happen at the site of tumour in e.g. lymphoma.
DIC can happen in treating acute myeloid leukaemia as well.
Explain why vomiting might occur in chemo.
Direct action of chemotherapy drugs on the central chemoreceptor trigger zone.
There are 3 patterns of emesis in chemo.
Acute phase 4-12 hours
Delayed onset 2-5 days later
Chronic phase - may persist up to 14 days
Give chemo drugs which will cause a lot of alopecia.
Doxorubicin
Vinca alkaloids
Cyclophosphamide
Give an example of a chemo with minimal alopecia.
Platinum compounds
What might help in alopecia due to chemo?
Scalp cooling where you wear a hat that cools down your head.
However this can be very uncomfortable and lead to migraines.
Give local skin toxicity conditions in chemo.
Irritation
Thrombophlebitis of veins
Give general skin conditions due to chemo.
Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores.
Which chemo drug might cause hyperkeratosis, hyperpigmentation and ulcerated pressure sores?
Bleomycin
What might busulphan, doxorubicin, cyclophosphamide and actinomycin D cause? (In terms of skin)
Hyperpigmentation
Where is mucositis most commonly worst?
In oropharynx
What does mucositis present as?
Sore mouth and throat
Diarrhoea
GI bleed
Which drugs might cause cardio-toxicity?
Doxorubicin
High dose of cyclophosphamide
What lung condition might bleomycin cause?
Pulmonary fibrosis
Why is it important to be aware of the patient being/have been on bleomycin if they come in with SOB and pulmonary fibrosis?
Giving oxygen will exacerbate the problem!
What is the most frequent cause of death from toxicity of chemo?
Haematological toxicity due to neutropenia and an increased risk of sepsis.
What factors will influence the dosing of chemo in a patient?
Surface area and/or BMI
Drug handling ability via liver function, renal function etc…
General wellbeing (performance status and comorbidities)
Why does the chemo treatment be in cycles?
To let the marrow and GI tract to recover between cycles.
What causes variability of pharmacokinetics in chemo?
Abnormalities in absorption, distribution, elimination and protein binding.
Give examples of abnormalities of absorption.
Nausea and vomiting
Compliance difficulties
Gut problems
Give examples of abnormalities of distribution.
Weight loss
Reduced body fat
Ascites
Give examples of abnormalities of elimination.
Liver and renal dysfunction.
Other medications
Give examples of abnormalities of protein binding.
Low albumin in e.g. malnutrition
Other drugs that may displace
Which drug interacts with vincristine?
Itraconazole (a common antifungal)
What can itraconazole interacting with vincristine lead to?
Neuropathy
What interacts with capecitabine (5-fluorouracil)?
Warfarin
St Johns wort
Grapefruit juice
What interacts with methotrexate?
Penicillin
NSAIDs
How can you monitor the cancer during the chemotherapy?
The response of the cancer
Drug levels
Checks for organ damage
How do you monitor the response of the cancer?
Radiological imaging
Tumour marker blood tests
Bone marrow/Cytogenetics
Give an example of drug monitoring.
Methotrexate drug assays taken on serial days to ensure clearance from the blood after folinic acid rescue.
What organ damage do you check for and how?
Creatinine clearance for kidneys.
ECG for cardio-toxicity
LFTs for liver function
Explain neoadjuvant treatment.
Given before surgery or radiotherapy for the primary cancer
Expain adjuvant treatment.
Given after surgery to excise the primary cancer, aiming to reduce relapse risk in e.g. breast cancer.
Explain palliative chemo.
Treat the current or anticipitated symptoms without curative intent.
Explain primary treatment.
1st line of treatment of cancer.
Explain salvage treatment.
Chemotherapy for relapsed disease.
