Metastatic prostate cancer

Question 1

What is abiraterone?

Answer 1

Oral androgen inhibitor for use in metastatic PC.

Question 2

What is abiraterone licensed for?

Answer 2

1st line meta PC treatment where chemotherapy is noy yet clinically indicated: pt asymptomatic.

Also: after failure of HT or CT.

Question 3

How does abiraterone work?

Answer 3

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.

Question 4

What must abiraterone be given with and why?

Answer 4

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.

Question 5

What is the enzyme that abiraterone blocks? is this reversible inhibition?

Answer 5

Abiraterone is an irrerversible inhibitor of CYP17A1 - enzyme responsible for androgen and cortisol production.

Question 6

What is the normal dose of abiraterone?

Answer 6

1g daily without food (decreased BA?)

Question 7

Abiraterone prolongs overall survivial by ___ months in pts who have had prior chemotherapy.

Answer 7

3-4 months.

overall survival 11-15

Question 8

What impact does abiraterone have on pain?

Answer 8

Reduces pain.

Question 9

Why does abiraterone need to be given with prednisolone?

Answer 9

It decreases cortisol leading to symptoms of cortisol deficiency such as hypertension, hypokalaemia, fluid retention.

Question 10

What are the side effects of abiraterone?

Answer 10

Peripheral oedema.
Hypokalaemia.
Hypertension. 
UTI
Elevated LFTs - monitor every 2 weeks for 1st 3 months.

Question 11

What is enzalutamide?

Answer 11

Potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. New hormonal treatment.

Question 12

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.

Answer 12

Enzalutamide.

Question 13

How often do LFTs need to be monitored for abiraterone?

Answer 13

Every 2 weeks for 3 months.

Question 14

CYP17A1 inhibitor

Answer 14

Abiraterone, irrerversible.

Must be given with a steroid.

Question 15

Potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. New hormonal treatment.

Answer 15

Enzalutamide

Question 16

How does enzalutamide work?

Answer 16

Inhibits androgens + androgen receptors, inhibits nuclear translocation of activated receptors -> reduced associated of activated androgen receptors with DNA.

Question 17

For what is enzalutamide licensed?

Answer 17

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.

Question 18

When would chemotherapy not yet be clinically indicated?

Answer 18

When patient is asymptomatic/mildly symptomatic (WHO PS 0-1)

Question 19

What are the side effects of enzalutamide?

Answer 19

Headache, 
Hot flushes, 
Memory problems
Visual hallucinations. 
Slightly increased risk of seizures.

Question 20

54% of patients on enzalutamide could achieve at least a __% reduction in PSA.

Answer 20

50%

Question 21

Overall survival on enzalutamide was ___months compated to 13.6 months with placebo.

Answer 21

18.4

Question 22

Chemotherapy would be used for

Answer 22

Metastatic disease which is refractory to hormone therapy/abiraterone/enzalutamide.

Question 23

What is the common chemotherapy regimen in metastatic PC?

Answer 23

Docetaxel and prednisolone.

Question 24

How does docetaxel work?

Answer 24

Disrupts microtubular network of cells during cell division, so mitosis cannot occur. Leading to cell death.

Question 25

What androgen blocker can cause visual hallucinations?

Answer 25

Enzalutamide:
Headache, 
Hot flushes
Memory problems
Visual hallucinations. 
Risk of seizures (slightly increased)

Question 26

What are the side effects of docetaxel + prednisolone?

Answer 26

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?)

Question 27

Patients need to take dexamethasone 8mg bd for __ days prior to starting a docetaxel and prednisolone regimen.

Answer 27

3 days.

Question 28

WRT to LFTs when would th dose of docetaxel be reduced?

Answer 28

If the function of liver is impaired.

Question 29

Before each dose of chemo, neuts must be _____ and platelets must be ____.

Answer 29

Before each dose of chemo, neut must be >1.5 and platelets must be >100.

Question 30

What antiemetics should be prescribed to those receiving docetaxel + prednisolone?

Answer 30

metoclopramide 10mg tds prn or domperidone (extra pyramidal side effects) 10mg tds prn.

Question 31

Whar are the pharmaceutical care issues wrt to docetaxel and prednisolone?

Answer 31

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