Treatment of Prostate Cancer Flashcards
What two almost equivalent sources of androgen must you take into account when targeting prostate cancer?
- Testicular and Local Testosterone and DHT
- Adrenal DHEA (dehydroepiandrosterone)
What is the 1st line of treatment in patients with prostate cancer?
1st line: Medical or Surgical Castration + Anti-androgen therapy
Radiation and Iodine coated titanium seeds can also be used
What GnRH analogs are used in chemical castration for prostate cancer?
GnRH agonists
Goserelin, Histrelin, Leuprolide, Triptorelin (the “relins”)
GnRH agonists
- Administration
- MOA
- Name Them
**GnRH agonists
Goserelin, Histrelin, Leuprolide, Triptorelin**
ADMINISTRATION
SC injection; monthly
_MOA_ Persistent Agonism (\> 2-4 weeks) of the GnRH receptor leads to increased FSH and LH levels (disease flare) followed by DOWNREGULATION of the receptor
What should Goserelin, Histrelin, Leuprolide, and Triptorelin be administered with to reduce side effects when initiating treatment?
**AR blockers can be used to block the initial flare
GnRH Agonists
- Name Them
- Adverse Effects
GnRH agonists
Goserelin, Histrelin, Leuprolide, Triptorelin
ADVERSE EFFECTS
All the effects of castration: Low Testosterone => Hot Flashes, Decreased Libido, ED, Gynecomastic, Osteoporosis
GnRH Agonists
Goserelin, Histrelin, Leuprolide, Triptorelin
- Indications
- Contraindications
INDICATION
Prostate cancer, Breast cancer (goserelin)
CONTRAINDICATION
Category X
What drug has an action opposite to that of Goserelin, Leuprolide, Histrelin, and Triptorelin?
Degarelix
GnRH Antagonist
- Name it.
- Administration
- MOA
Degarelix
ADMINISTRATION
SC injections
MOA
Reversible agent, blocks GnRH, clearly no surge with this drug
Degarelix
- Adverse Effects
ADVERSE EFFECTS
All the effects of castration: Low Testosterone => Hot Flashes, Decreased Libido, ED, Gynecomastic, Osteoporosis
Degarelix
- Indication
- Contraindication
INDICATION
Prostate cancer, Breast cancer (goserelin)
CONTRAINDICATION
Category X
Estramustine
- Administration
- MOA
Estramustine
ADMINISTRATION
Oral
MOA
Steroidal drug that targets Estramustine Binding Protein (EMBP) on prostate cancer, in doing so it brings an alkylator that functions as a microtubule inhibitor => G2/M arrest and DNA strand Breakage
**ALSO this produces circulating levels of estrodiol comparable to those seen in women’s estrogen therapy. Estrogen feedback on HPG axis further reduces testosterone**
Estramustine
- Adverse Effects
Estramustine
ADVERSE EFFECTS
Similar Stucture to Estogen leads to “feedback-like” inhibition of the HPG axis
Estrogen-like effects: Gynecomastia, ED, Thromboembolism (similar to estrogen therapy), Stroke, Edema
Hepatic Effects: Elevated Hepatic Enzyme, Hyperbilirubinemia
Estramustine
- Indication
- Contraindication
Estramustine
INDICATION
Prostate Cancer
CONTRAINDICATION
None stated, but probably watch out giving this to people with prior-existing CV risk factors
What Androgen Receptor Blockers are used in the treatment of Prostate cancer?
Androgen Receptor Blockers
Bicalutamide, Enzalutamide, Flutamide, Nilutamide – the “lutamides”
Androgen Receptor Blockers
- Name them
- Administration
- Adverse Effects
Androgen Receptor Blockers
Bicalutamide, Enzalutamide, Flutamide, Nilutamide – the “lutamides”
ADMINISTRATION
Oral - daily
MOA
Blockage of androgen receptors to prevent receptor stimulation on cancer cells. Administered concurrently with GnRH agonist
Bicalutamide, Enzalutamide, Flutamide, Nilutamide
- Adverse Effects
Androgen Receptor Blockers
Bicalutamide, Enzalutamide, Flutamide, Nilutamide – the “lutamides”
ADVERSE EFFECTS
Castration Effects: Hot flashes, decreased libido, ED, gynecomastia, osteoporosis
Teratogens
Bcalutamide, Enzalutamide, Flutamide, Nilutamide
- Indications
- Contraindications (exceptions?)
Androgen Receptor Blockers
Bicalutamide, Enzalutamide, Flutamide, Nilutamide – the “lutamides”
INDICATION
Prostate Cancer
FLUTAMIDE ALSO USED TO TREAT HIRSUTISM OR POLYCYSTIC OVARIAN SYNDROME
CONTRAINDICATION
Category X, exceptor nilutamide – Category C
What anti-hypertensive drug can also be used in the treatment of prostate cancer?
- how so?
Spironolactone - works as an androgen receptor blocker
What drug is used as immunotherapy against prostate cancer?
Sipuleucel - T
Sipuleucel-T
- Administration
- MOA
Sipuleucel-T
ADMINISTRATION
IV
MOA
Patients WBC’s including APCs are removed and cultured with GM-CSF + PAP (prostate acid phosphatase) => The APCs take up the antigen and express it on their surface to T, B, and NK cells. These products are then reinfused into the patient.
Sipuleucel-T
- Adverse Effects
- Indication
Sipuleucel-T
ADVERSE EFFECTS
Mild infusion reactions; fever/chills/dyspnea; GI effects
Paresthesias, Citrate Toxicity, and fatigue
INDICATION
Prostate Cancer
A previously normotensive man comes in for a check up on his prostate cancer therapy and his blood pressure is now 150/95. What drug is he likely recieving?
Abiraterone - blocks 17-alpha hydroxylase and shunts all pregnenolone to become aldosterone leading to a hypermineralocorticoid state
Abiraterone
- MOA
CYP17 (17-alpha-hydroxylase) inhibitor, prevents Cholesterol from getting turned into adrogen
Abiraterone
- Adverse Effects
- Problems with quick withdrawal?
**Abiraterone
AEs:
- HTN, Hypokalemia, Fluid Retention => may exacerbate previously existing CV issues
IF WITHDRAWN too quickly adrenal insufficiency (hypotension, tachycardria, hyperkalemia) may occur
Check LFTs, because they become elevated
TERATOGEN**
Why should males taking Abiraterone wear condoms?
- what other precautions should be taken?
**Because this drug is pregnancy category X males should wear condoms and women shouldn’t handle the drug
What are the risks and benefits of using estrogens to inhibit estrogen and testosterone release in Prostate Cancer?
Estrogens
Advantages: Osteoprotective
Disadvantages: None really, because transdermal estrogen administration prevents CV effects (DVT, thromboembolism)
If estrogen is used in the treatment of prostate cancer, what is the best way to administer it?
Estrogens
Transdermal estrogens can be given to men to prevent LH (and FSH) release.
What is the use of Finasteride and Dutasteride in prostate cancer?
Finasteride, Dutasteride
ADMINISTRATION
PO
MOA
Inhibition of 5 alpha reductase prevents DHT formation (androgen believed to be implicated in proliferation of prostate cancer). HOWEVER, the location and expression level of the enzyme cannot predict the degree of testosterone metabolism to DHT (variation could be polymorphisms). Effects of DHT are believed to be related to off-target effects.
What class of chemotherapeutics is used in Conventional prostate chemotherapy?
Taxanes: Docetaxel, Carbaitaxel
What do you need to administer before infusing taxanes?
**Patients must be pre-medicated with Corticosteriods and anti-histamines to prevent infusion reactions associated with these drugs given that they often contain surfactant in their preparation**
How does Carazitaxel differ from other taxanes?
- *Carbazitaxel**
- *Differs from other taxanes** in that it is not a good substrate for Pgp. This makes it good for tx of multidrug resistant tumors. It can also penetrate the BBB (given its ability to not get effluxed by Pgp that is heavily expressed at the BBB).
