prostate cancer 2

Question 1

Abiraterone

Answer 1

Indication may change soon

For metastasis, but can be either castrate resistant or sensitive (as long as metastasis)

Micrometastasis for castrate snesitive, didn’t get picked up but it is not cuz the cancer cells found way to overcome testosterone

• Indicated for metastatic prostate cancer
• First indication was metastatic castrate resistant prostate cancer (metCRPC)
• Recently acquired indication for metastatic castrate sensitive prostate cancer (metCSPC)
• Used in combination with ADT (LHRH analog or orchiectomy)
• MOA:
• Selective irreversible CYP17 enzyme inhibitor
• Active in testicular, adrenal, and prostate tumour tissue
• Dose: 1000 mg po daily
• Available as 250 mg tablets (4 tabs daily) or 500mg tablets (2 tabs daily)
• Administer on EMPTY stomach (bioavailability increased with food)
• Drug Interactions:
• CYP 3A4 - SUBSTRATE
• CYP 2D6 - STRONG INHIBITOR

Question 2

Treatment for Metastatic Prostate Cancer

• Goals of care:
• slow progression, quality of life, symptom management
• Palliation

Answer 2

• Supportive Care
• Pain Control if Metastasized – usually bone:
• Radiation
• Chemotherapy
• Analgesics (opioids)
• Bisphosphonates for pain control of bone metastases

Pharmacotherapy Options:
* CYP17 inhibitors (abiraterone)
* Novel antiandrogens (enzalutamide or apalutamide)
* Chemotherapy (taxanes)
* Docetaxel
* Cabazitaxel

Question 3

• Adverse Effects:

Answer 3

• Diarrhea (approximately 20%)
• Elevated liver function tests
• Monitor for Hepatotoxicity
• Mineralocorticoid effects due to
  compensatory increase in ACTH:
• Peripheral edema (25%)
• Hypertension (10-20%)
• Hypokalemia (15%)
• Monitor BP, K+, cholesterol
• Abiraterone is usually administered
  with prednisone (5 mg twice daily)

Question 4

why do you see prednisone with abiraterone

Answer 4

If we block CYP 17 in all tissues (adrenals, testes)
We block creation of cortisol and testorerone

ACTH is driven up which increases aldosterone high mineralcorticoid

We have to give them prednisone 5mg BID
Increase in ACTH
drives
mineralocorticoid
pathway to increase

will see Peripheral edema (25%)
* Hypertension (10-20%)
* Hypokalemia (15%)

Question 5

Where Does Chemo Fit?
Docetaxel + Prednisone

• Dosing Regimen =
• Docetaxel 75mg/m2 IV q21days X 6 cycles
• Prednisone 5 mg po bid (augments efficacy for palliation and tumour
  response)

Answer 5

• Taxane Chemotherapy
• Place in therapy:
• Metastatic Disease (Palliative intent/goals of therapy)
• Good efficacy for pain reduction in metastatic disease
• Metastatic Castrate Sensitive Prostate Cancer (castration-naïve, met-CSPC)
• Docetaxel can improve overall survival in patients about to start or have recently started
  ADT (CHAARTED trial)
• Metastatic Castrate Resistant Prostate Cancer (met-CRPC)
• Therapy option along with abiraterone or enzalutamide
• Abiraterone or enzalutamide preferred if patient has already had docetaxel

prednisone augments response

• Adverse effects:
• Myelosuppression
• Fluid retention
• Hypersensitivity reactions
• Remember dexamethasone pre (reduce fluid retention, hypersens)

Question 6

Sequencing of therapies in CRPC

Answer 6

• Abiraterone:
• Evidence of improved PFS and extended time to initiation of chemotherapy
  and time to onset/worsening of pain if pre-docetaxel
• Evidence of extended survival after docetaxel
• Enzalutamide:
• Evidence of improved PFS and OS (in docetaxel naïve met-CRPC patients)
• Evidence of improved metastasis free survival over placebo (37 mo vs 15 mo) in patients with regional CRPC
• Docetaxel + Prednisone
• Docetaxel can improve overall survival in patients about to start or have
  recently started ADT (CHAARTED trial)

Question 7

Therapeutic Options in Metastatic CRPC
NOVEL = in addition to leuprolide

Answer 7

No prior novel hormone therapy AND no chemotherapy
Docetaxel
Abiraterone
Enzalutamide

Prior Novel Hormone
Therapy ONLY
Docetaxe

Prior Docetaxel (chemotherapy) ONLY
Abiraterone
Enzalutamide
Cabazitaxel (2nd line, not covered in class)

Prior Chemotherapy AND prior Novel Hormone
Therapy

Cabazetaxel
Possibly
docetaxel again if
responded well
before and
sufficient time
has passed

Question 8

t aTherapeutic Options in Metastatic CSPC

Answer 8

just add apalutamide to what u would do for CSPC

Question 9

monitorinh

Answer 9

• PR is started on abiraterone 1000mg po daily and Prednisone 5 mg po BID
• The pharmacist provides the following information as part of the
  medication counselling:
• Abiraterone - Take 4 tablets daily on an empty stomach
• Prednisone – Take 1 tablet twice daily with food
• Monitor your bowel movements as diarrhea can occur in 1 in 5 patients on
  abiraterone
• Regular blood tests are important to monitor your liver, your potassium level, and
  your cholesterol level
• Swelling, fluid retention, and an increase in blood pressure can occur. Try to put your
  feet up when needed and check your blood pressure regularly.
• Please be sure to talk to me or another pharmacist prior to taking any other
  medications as abiraterone has several drug interactions.

Question 10

Localized Disease (Stage I, II, III)

Answer 10

see slide 54