Table 1.
Therapeutic classes and agents approved for prostate cancer, October 2020
| Class | Target | Agent | Mechanism of action | Indication(s) | Notable side effects |
|---|---|---|---|---|---|
| Nonsteroidal androgen receptor antagonist (first generation) | Androgen receptor | Bicalutamide, flutamide, nilutamide | Competitively and reversibly inhibit binding of testosterone and DHT to ligand binding domain of androgen receptor | In combination with GnRH agonists in metastatic disease | Hot flashes, pain, infection, abdominal pain |
| Nonsteroidal androgen receptor antagonist (second generation) | Androgen receptor | Apalutamide, darolutamide, enzalutamide | Competitively and reversibly inhibit binding of testosterone and DHT to ligand binding domain of androgen receptor & downstream inhibition of AR translocation to nucleus from cytoplasm, recruitment of coactivators and binding to DNA |
CRPC,a mCSPC,b nmCRPC,c (in combination with ADTc) | Fatigue, hypertension, seizures (enzalutamide), arthralgia, nausea, hot flashes |
| Androgen biosynthesis inhibitor | Steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase) | Abiraterone | Abiraterone acetate (prodrug) converted in vivo to abiraterone which inhibits CYP17A1 expressed in adrenal, testicles and prostate tumor | mCRPC, mCSPC (in combination with prednisone and ADT) | Hypokalemia, hypertension, edema, adrenal insufficiency, hepatotoxicity |
| GnRH antagonists | GnRH receptor | Degarelix, relugolix | Competitively and reversibly inhibit GnRH receptors in pituitary gland which blocks release of FSH and LH | Advanced prostate cancer | Injection site reaction (degarelix), hot flashes, fatigue, weight gain, hepatotoxicity |
| GnRH agonists | GnRH receptor | Histrelin, goserelin, leuprolide, triptorelin | Continuous stimulation of GnRH receptor that leads to initial surge in FSH, LH, testosterone, and DHT followed by reductions | Advanced prostate cancer (including mCRPC) | General pain, hot flashes and sweating, gastrointestinal disorders |
Note that not all agents in a given class are approved for all indications of their class. Castration
a Resistant prostate cancer.
b Metastatic castration sensitive prostate cancer.
c Nonmetastatic castration resistant prostate cancer.
d Androgen deprivation therapy.