PA30326 Workshop Prostate

Question 1

Mr PC, a 69 yr old male presented with urinary frequency, nocturia, pain in his lower back and increasing lethargy over the previous 3 months. His past medical history was unremarkable. He was overweight and admitted to eating a high fat diet. On PR examination there was a hard suspicious nodule on his prostate and urinalysis revealed a trace of blood. His haemoglobin was 10g/dL and serum PSA was 155ng/ml. X-ray of his spine showed sclerotic changes in some vertebrae. A needle biopsy of his prostate was performed under antibiotic cover, and histology confirmed the presence of a Gleason Grade 7 carcinoma. A radiolabelled bone scan showed multiple areas of increased uptake in the ribs and spine. The patient was commenced on bicalutamide 50mg PO od for 3 weeks and 7 days later was given goserelin 3.6mg SC.

What symptoms did Mr PC have that made his GP suspect prostate cancer?

Does Mr PC have any risk factors for prostate cancer?

Answer 1

Symptoms

• Urinary frequency
• Nocturia
• Lower backpain
• Lethargy

Risk factors

• High fat diet
• Age

Question 2

What is PSA and how is it used in prostate cancer?

Answer 2

PSA
- Glycoprotein released by prostate gland to aid liquification of semen

• Increases in prostate cancer as it leaks through cancer cell membrane into serum
• Used to diagnose prostate cancer & monitor response to therapy

Question 3

How does bicalutamide work?

Answer 3

Androgen blocker

- Competes with DHT & blocks its production os no active metabolites

Question 4

Why was bicalutamide continued after goserelin was given?

Answer 4

To cover period of tumour flare & worsened symptoms

• Goserelin is LHRH agonist which initially provides stimulus for LH production & androgen production
• After few weeks receptors become desensitised and LH is not stimulated

Question 5

If you were handing out Mr PC’s prescription for bicalutamide & goserelin, what information would you tell him about these medicines?

Answer 5

• Start taking Bicalutamide then have goserelin inj at GP surgery on day 7
• Continue Bicalutamide for 2 weeks after goserelin
• Side effects of Bicalutamide
  : hot flushes, impotence, loss of libido, breast tenderness, fatigue

Question 6

3 months later Mr PC returned to his GP for a check-up. His PSA had dropped to 20, his pain and lower urinary tract symptoms had settled. He was reassured that his disease was responding to hormonal therapy, and continued to attend 3-monthly check-ups. Unfortunately, about 18 months after he was first diagnosed, his PSA started to climb and his lower urinary tract symptoms returned, and his GP referred him to the Oncologist at the local hospital.
The Oncologist confirmed that Mr PC’s cancer had become hormone-refractory, and it was decided to start him on abiraterone and prednisolone treatment.

Why is prednisolone needed in this regimen?

Answer 6

• Abiraterone can lower blood cortisol level because it is a CYP17A1 inhibitor
• Cortisol biosytnehsis requires activation of CYP17A1 so when its blocked cortisol levels drop and there is compensatory increase in ACTH which results in accumulation of steroids with mineralcorticoid properties upstream of CYP17A1 in cortisol biosynthesis pathway
• This can cause effects such as hypertension, hypokalaemia and fluid retention

Question 7

What are the possible side effects of abiraterone & prednisolone?

Answer 7

• Peripheral oedema
• Hypokalaemia
• Abnormal LFTs
• UTI
• Hypertension

Question 8

What action should be taken if a patient’s ALT level rises to 500 during treatment with abiraterone?

Answer 8

Normal ALT = 15-60
500 is approx 8x higher

Withhold abiraterone until ALT back to baseline then restart at 500mg od

Question 9

Mr PC had a good response to abiraterone and his PSA and symptoms were well controlled for another 18 months. After this time his PSA begins to increase and he was suffering from back pain from his bony metastases. He was keen for further treatment so it was decided to start him on chemotherapy with docetaxel and prednisolone.

You are the pharmacist prescriber. Given the following information, what dose of docetaxel would you prescribe for the first cycle for Mr PC?

Answer 9

• 150mg

Question 10

What are the likely side effects of this chemotherapy regimen?
- Docetaxel and Prednisolone

Answer 10

• Headache
• Memory impairment
• Anxiety
• Restless legs
• Risk of seizure (1%)
• Fatigue