Leuprolide
Lupron
GnRH agonist – stimulate negative feedback mechanism; 2-3 weeks to realize decrease in testosterone production
MOA: GnRH agonist —> Decreased LH/FSH —> Decreased Testosterone —> Decreased Prostate Cancer Growth
TOX: ECG changes, peripheral edema, hot flashes, weakness, Bone pain
Goserelin
Zoladex
GnRH agonist – stimulate negative feedback mechanism; 2-3 weeks to realize decrease in testosterone production
MOA: GnRH agonist —> Decreased LH/FSH —> Decreased Testosterone —> Decreased Prostate Cancer Growth
TOX: ECG changes, peripheral edema, hot flashes, weakness, Bone pain
Degarelix
Firmagon
GnRH antagonist – directly blocks pathway
MOA: GnRH antagonist —> Decreased LH/FSH —> Decreased Testosterone —> Decreased Prostate Cancer Growth
TOX: injection related reactions (SubQ), hot flashes, weight gain
Flutamide
Eulexin
MOA: Block androgen receptor (competitive inhibitor)
↑ estrogen release (potential for gynecomastia)
TOX: gynecomastia, ↓ libido, diarrhea, nausea, liver abnormalities
Nilutamide
Nilandron
single daily oral dose is effective
MOA: Block androgen receptor (competitive inhibitor)
↑ estrogen release (potential for gynecomastia)
TOX: gynecomastia, ↓ libido, diarrhea, nausea
visual disturbances, alcohol intolerance
Bicalutamide
Casodex - highest affinity = lowest risk of toxicities (out of Flutamide, Nilutamide, Bicalutamide)
single daily oral dose is effective
MOA: Block androgen receptor (competitive inhibitor)
↑ estrogen release (potential for gynecomastia)
TOX: gynecomastia, ↓ libido, diarrhea, nausea
Enzalutamide
Xtandi - strongest/highest affinity out of the 4
Single once daily dose
MOA: Androgen receptor (AR) competitive inhibitor —> Blocks trans-location of AR to nucleus and interaction of AR with DNA
- Avoid use with CYP2C8, CYP3A4 inhibitors
TOX: Risk of seizures (CNS penetration – through GABA(a) inhibition)
Pregnancy category X
Abiraterone Acetate
Zytiga - inhibitor of steroid synthesis - oral - once daily
[adrenal gland, testes, prostate cancer cells]
MOA: inhibits CYP17A1 (17α-hydroxylase and 17,20-lyase) —> ↓ Testosterone production —> decreases in levels of DHEA, testosterone, and dihydrotestosterone (DHT).
- highly protein bound (>99%)
- metabolised in the liver by CYP3A4 and SULT2A1 to inactive metabolites
- excreted in feces (~88%) and urine (~5%)
TOX: Joint swelling, hypokalemia, muscle discomfort, Hypertension, Hot flushes
Estramustine
Emcyt
Selective uptake into prostate cells (decrease in cytotoxic effects of non-prostate cells)
MOA: Binds to β-tubulin and microtubules —> Microtubule disassembly —> arrests prostate cancer cells in the G2/M phase
TOX: Myelosuppression
SEs: Hypercalcemia HSR → angioedema Gynecomastia ***↑ risk of thrombosis*** Fluid retention
Tamoxifen
Nolvadex (tablets) / Soltamox (oral solution)
- competitive partial agonist inhibitor of estradiol at the estrogen receptor
MOA: Formation of active metabolites (through 2D6) — N-desmethyltamoxifen + 4-hydroxytamoxifen (more potent for ER)
- Antagonist in breast tissue
- Agonist in bone, liver and endometrium
- – Increase in bone density
- – Decrease production of cholesterol in liver
- – Increase proliferation of endometrial cells -> endometrial/ovarian cancer
TOX: Increased risk of thrombosis, hot flashes, menstrual irregularities, vaginal bleeding
Raloxifene
Evista
- competitive partial agonist inhibitor of estradiol at the estrogen receptor
MOA: Antagonist in breast and uterus (endometrial cells)
— Compared to tamoxifen
Agonist in bone, liver
- – Increase in bone density
- – Decrease production of cholesterol in liver
TOX: Increased risk of thrombosis, hot flashes, leg cramps
Megestrol
Megace - Inhibition of Pituitary gonadotropin release (↓ estrogen secretion) - Agonist bind to progesterone receptor - Turns off estrogen-responsive genes - Partial Agonist at androgen receptor Antagonist = anti-androgenic effect - Agonist at glucocorticoid receptor --- Cushing’s --- Adrenal insufficiency
-Renal excretion
Toxicity – weight gain, thromboembolism, nausea, vomiting, glucose intolerance
pregnancy category X
Anastrozole
Arimidex - Non-steroidal MOA: Aromatase (P4502C19) inhibitors (decreased estrone/estradiol) ***Placenta, ovaries - Bind reversibly to heme
TOX: vaginal bleeding, hot flashes, hair thinning, nausea
Decrease bone density
Letrozole (hot flashes, hair thinning, nausea)
Letrozole
Femara
MOA: Aromatase (P4502C19) inhibitors (decreased estrone/estradiol)
***Placenta, ovaries
- Bind reversibly to heme
TOX: hot flashes, hair thinning, nausea
Exemestane
Aromasin
- Aromatase inhibitor (P4502C19)
MOA: ***irreversibly inactivates P4502C19 via reactive intermediate formation
TOX: vaginal bleeding, hot flashes, nausea, fatigue