Prostate cancer EXAM 3 Flashcards
What are the risk factors for Prostate cancer?
-Age
-Race: high with African Americans, low with Asians
-genetics
-environment: high-fat, cadmium exposure, testosterone, low vitamin D intake
Where is most of the Testosterone produced in men?
Testes (95%)
Adrenal gland (5%)
Which hormone causes the prostate to grow?
Dihydrotestosterone (DHT)
Which hormone stimulates the Pituitary gland? Which hormones are then secreted by the Pituitary gland?
LHRH (GnRH)
the pituitary gland then secrets FSH and LH
What are the targets of drug therapy in prostate cancer?
- LHRH (luteinizing hormone-releasing hormone) and GnRH (gonadotropin RH)
- Testosterone (either from the adrenal gland or testes)
- Adrenal receptors
What is the Gleason Score?
Staging of prostate cancer after prostate biopsy from different parts of the prostate
-the higher, the more aggressive
Which patient population has the highest risk of mortality from prostate cancer?
younger patients and high Gleason score
When should patients be screened for prostate cancer?
age 55-69, shared decision-making if they need screening
PSA screen at 55 for high-risk men
-African-Americans
-strong family history
What is the treatment approach for localized prostate cancer?
-Surgery
-Radiation
-Active Surveillance (treat if PSA goes high)
What is the treatment approach for metastatic prostate cancer?
-Anti-androgen therapy (ADT)
+/- chemotherapy
or
-Anti-androgen therapy (ADT)
+ enzalutamide or abiraterone (Antiandrogens)
What are the 4 options of Androgen deprivation therapy (ADT)?
-Orchiectomy (surgical castration)
-LHRH (GnRH) Agonists
-LHRH (GnRH) Antagonist
-Antiandrogens (NOT as monotherapy, added to LHRH agonist/antagonist))
What is the Goal serum testosterone after ADT?
(medical castration level)
< 50 ng/dL
(normal: 300 – 900 ng/dL)
What is the chemotherapy of choice in prostate cancer and when would Chemotherapy be considered?
Docetaxel (Taxotere) + ADT if high-volume disease
(chemo is not the #1 choice)
-androgen-independent prostate cancer
-hormone-refractory prostate cancer
-> Prostate grows despite low testosterone
What is the first-line therapy for prostate cancer? How do these drugs work?
LHRH Agonists
-Leuprolide
-Goserelin
-they cause a negative feedback loop leading to suppression of LH and FSH secretion
-> NO Testosterone secretion by the testes
What might happen during the first weeks of treatment of prostate cancer?
tumor flare bc testosterone level initially goes up -> causing the prostate to grow initially
-hot flashes
-ED
-libido goes down
-bone pain (if bone metastasis) -> can cause spinal cord compression and permanent urinary incontinence or paralysis
-prostate pain
Which drugs may be used to block the “tumor flare” during the first 2 weeks?
Antiandrogens
-especially in patients with lesions involving the spinal cord (can cause urinary incontinence or paralysis)
What are the LHRH antagonists?
Degarelix (IV)
Relugolix (PO)
What are the benefits of LNRH antagonist?
They are safer in the first 2 weeks (long-term as efficient as LHRH agonists)
-bc they don’t cause the “tumor flare” since no LH and FSH stimulation
Name the Antiandrogens.
don’t need to know brand names
New gens: used for prostate cancer treatment
Enzalutamide
Apalutamide
Darolutamide
old-gens: used to block the “tumor flare”
-Bicalutamide
-Flutamide
-Nilutamide
Which drug is used to block the “tumor flares” during the first weeks of prostate cancer therapy with LHRH agonists?
Bicalutamide (old gen Antiandrogen)
Antiandrogen can be used as monotherapy for prostate cancer therapy. T/F
!!!
False.
Need to be paired with LHRH agonists or antagonist
What is the side effect profile of antiandrogens?
-decreased libido
-irritability
-fatigue
-gain weight
-glucose and lipids increase
-depression
-hot flashes
-loss in bone mineral density (since we indirectly block estrogen, testosterone is converted into estrogen)
Which drug interaction is associated with new-gen Antiandrogens Enzalutamide and Apalutamide?
potent 3A4 incudcer
(Darolutamide is a wek 3A4 inducer)
Which of the Antiandrogens has seizure and headache in its side effect profile?
Enzalutamide
This new drug may interact with your anticoagulant, increasing your risk of a stroke.
What are ideal candidates for ADT intermittent treatment?
-low risk (low Gleason score)
-short-life expectancy
-don’t tolerate ADT well
What are ideal canditates for ADT continous treatment?
-average risk
-average life expectancy
What are ideal candidates for ADT + Antiandrogens/docetaxel?
-great performance status (otherwise healthy)
-high volume disease (>4 bone metastasis)
Which drugs are used for bone metastasis to reduce the risk of skeletal-related events (SLE) and slow the cancer in the bone?
Know the dose
-Zoledronic acid 4 mg IV q 4-12 weeks
-Pamidronate 60-90 IV q 4-12
also give Calcium (500 mg) + Vit D (400 IU, helps with absorption of calcium)
Toxicities of Bisphosphonates
-Osteonecrosis of the jaw
-monitor SCr
Benefits/downside of Denosumab vs. bispohpsonates
Denosumab is more potent but has higher toxicity
Denosumab has a risk of rebound fraction when stopping it
-bisphosphonates stay longer in the bones even after stopping (no risk for rebound bone fraction)
MOA of Denosumab
MOA: RANK-ligand inhibitor -> prevents osteoclast activity
What is the dose of Denosumab in the prevention of bone metastasis in prostate cancer?
120 mg SC q 4 months
What is the dose of Denosumab in the treatment of ADT-induced bone loss in prostate cancer?
60 mg SC q 6 months
What is the MOA of Abiraterone (Zytiga)
CYP17 (adrenal enzyme) inhibitor
What is the function of CYP17?
found in the adrenal glands and it helps to produce testosterone
When might Abiraterone be used for prostate cancer?
-androgen-independent prostate cancer
-hormone-refractory prostate cancer
-> Prostate grows despite low testosterone, bc the adrenal gland starts producing more testosterone
How should Abiraterone be taken?
!!!
on empty stomach
with food, it would increase absorption (1000x)
Which side effects are associated with Abiraterone?
-Mineralocorticoid excess (hypertension, ↓ K, edema) - think opposite of spironolactone
(fluid retention and swelling)
-Adrenal insufficiency
-Hepatotoxicity due to CYP17 in the liver (monitor LFTs)
Which drug should be taken with Abiraterone, and why?
!!!
Prednisone
-helps prevent Mineralocorticoid excess
Abiraterone is known for which type of CYP interaction?
-it is CYP3A4 substrate: avoid 3A4 inhibitor/inducer
-it is a CYP2D6 inhibitor
common CYP substrates in this patients are Carvedilol and metoprolol !!!!
-> Hypotension !!!!
What is the consequence of blocking CYP17? Which molecules are affected?
- decrease in Cortisol -> leads to positive feedback of ACTH
- increase in Mineralocorticoids (Deoxycorticosteron and Corticosterone)
- side effects: hypokalemia, HTN, fluid overload, suppression of renin
How does Prednisone help with Abiraterone symptoms?
it replaces the Cortisol which would cause the positive feedback of ACTH and Mineralocorticoids (Deoxycorticosterone and Corticosterone)
Which disease contraindicates the use of Abiraterone?
heart failure
because of the side effects:
HTN
fluid overload
Which diseases are harder to control with LNRH antagonists
HTN
Hyperlipidema
diabetes
need to manage other chronic diseases, bc they may get worse with ADT treatment
Which drug might be considered if docetaxel doesn’t work?
-Cabazitaxel
-Radium-223 (ɑ-radiation) it concentrates where Ca2+ is -> targets bone metastasis
Which drug might be considered for prostate cancer prevention?
5-reductase inhibitors (finasteride)
for patients with PSA < 3.0 ng/ml, discuss with the doctor
not recommended bc higher rates of high-Gleason score cancer (aggressive tumor)
