Metastatic prostate cancer Flashcards
What is abiraterone?
Oral androgen inhibitor for use in metastatic PC.
What is abiraterone licensed for?
1st line meta PC treatment where chemotherapy is noy yet clinically indicated: pt asymptomatic.
Also: after failure of HT or CT.
How does abiraterone work?
Inhibits androgen production from testes, adrenal gland and prostate tumour cells - all 3 sources of androgens in the body.
It is an irreversible inhibitor of CYP17A1 the enzyme responsible for androgen and cortisol production.
What must abiraterone be given with and why?
Must be given with a steriod (prednisolone 5mg PO bd).
Decreased cortisol causes a response by the hypothalamus that increases ACTH levels and the symptoms of cortisol deficiency e.g. Hypertension, fluid retention.
What is the enzyme that abiraterone blocks? is this reversible inhibition?
Abiraterone is an irrerversible inhibitor of CYP17A1 - enzyme responsible for androgen and cortisol production.
What is the normal dose of abiraterone?
1g daily without food (decreased BA?)
Abiraterone prolongs overall survivial by ___ months in pts who have had prior chemotherapy.
3-4 months.
overall survival 11-15
What impact does abiraterone have on pain?
Reduces pain.
Why does abiraterone need to be given with prednisolone?
It decreases cortisol leading to symptoms of cortisol deficiency such as hypertension, hypokalaemia, fluid retention.
What are the side effects of abiraterone?
Peripheral oedema. Hypokalaemia. Hypertension. UTI Elevated LFTs - monitor every 2 weeks for 1st 3 months.
What is enzalutamide?
Potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. New hormonal treatment.
Inhibitor of the binding of androgens to androgen receptors, inhibitor of nuclear translocation of activated receptors and thus reduced associated of activated androgen receptors with DNA.
Enzalutamide.
How often do LFTs need to be monitored for abiraterone?
Every 2 weeks for 3 months.
CYP17A1 inhibitor
Abiraterone, irrerversible.
Must be given with a steroid.
Potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. New hormonal treatment.
Enzalutamide
How does enzalutamide work?
Inhibits androgens + androgen receptors, inhibits nuclear translocation of activated receptors -> reduced associated of activated androgen receptors with DNA.
For what is enzalutamide licensed?
Metastatic prostate cancer 1st line where chemotherapy is not yet clinically indicated.
Also for treatment of metastatic prostate where disease has progressed on or after docetaxel therapy.
When would chemotherapy not yet be clinically indicated?
When patient is asymptomatic/mildly symptomatic (WHO PS 0-1)
What are the side effects of enzalutamide?
Headache, Hot flushes, Memory problems Visual hallucinations. Slightly increased risk of seizures.
54% of patients on enzalutamide could achieve at least a __% reduction in PSA.
50%
Overall survival on enzalutamide was ___months compated to 13.6 months with placebo.
18.4
Chemotherapy would be used for
Metastatic disease which is refractory to hormone therapy/abiraterone/enzalutamide.
What is the common chemotherapy regimen in metastatic PC?
Docetaxel and prednisolone.
How does docetaxel work?
Disrupts microtubular network of cells during cell division, so mitosis cannot occur. Leading to cell death.
What androgen blocker can cause visual hallucinations?
Enzalutamide: Headache, Hot flushes Memory problems Visual hallucinations. Risk of seizures (slightly increased)
What are the side effects of docetaxel + prednisolone?
BM suppression.
Severe alopecia - older men tend to be bald/not care.
Nause & vomting - low emetogenic potential.
Myalgia/arthralgia.
Fluid retention and hypersensitivity. (Premed with dexamethasone?)
Patients need to take dexamethasone 8mg bd for __ days prior to starting a docetaxel and prednisolone regimen.
3 days.
WRT to LFTs when would th dose of docetaxel be reduced?
If the function of liver is impaired.
Before each dose of chemo, neuts must be _____ and platelets must be ____.
Before each dose of chemo, neut must be >1.5 and platelets must be >100.
What antiemetics should be prescribed to those receiving docetaxel + prednisolone?
metoclopramide 10mg tds prn or domperidone (extra pyramidal side effects) 10mg tds prn.
Whar are the pharmaceutical care issues wrt to docetaxel and prednisolone?
Check BSA & doses against protocol
Check FBC – neuts ≥ 1.5 & plts ≥ 100 before each course of chemo
Ensure pt has taken pre-med (dexamethasone 8mg bd for 3 days starting day before chemo)
Check LFTs – ↓ docetaxel dose if impaired
Ensure antiemetics for mild to moderately emetogenic chemo prescribed e.g. metoclopramide 10mg tds prn or domperidone 10mg tds prn
Ensure patient understands when to take dexamethasone & prednisolone & that both are steroids
