Editing Hormonal Therapy (section)

====== Second-generation: enzalutamide, apalutamide, darolutamide ======
* '''<span style="color:#ff0000">Enzalutamide</span>'''
** '''<span style="color:#ff0000">MOA: irreversibly binds directly to the androgen receptor and inhibits the binding of androgens, AR nuclear translocation, and AR–mediated DNA binding</span>'''
** '''<span style="color:#ff0000">Contraindications</span>'''
***'''<span style="color:#ff0000">History of seizures</span>'''
**'''<span style="color:#ff0000">Adverse events (note that first 6 also apply to apalutamide:</span>'''
**# '''<span style="color:#ff0000">HTN</span>'''
**# '''<span style="color:#ff0000">Diarrhea</span>'''
**# '''<span style="color:#ff0000">Fatigue</span>'''
**# '''<span style="color:#ff0000">Seizures</span>'''
**#* '''<1% of patients in clinical trials'''
**# '''<span style="color:#ff0000">Falls</span>'''
**# '''<span style="color:#ff0000">Fracture</span>'''
**# '''<span style="color:#ff0000">Hot flashes</span>'''
**# '''Neutropenia'''
**# '''Memory impairment'''
**# '''Arthralgia'''
** '''Recommended clinical monitoring (as per Cancer Care Ontario (accessed March 2020))'''
*** '''Blood pressure: baseline and each visit'''
*** '''ECG and electrolytes: Baseline and at each visit, in patients at risk of QT prolongation'''
*** '''INR monitoring for patients on warfarin: baseline and at each visit'''
*** '''Clinical assessment of adverse events: at each visit'''
** '''Trials with enzalutamide'''
*** '''AFFIRM: post-docetaxel mCRPC'''
*** '''PREVAIL: pre-docetaxel mCRPC'''
*** '''PROSPER: M0 CRPC'''
*** '''ENZAMET: M1 CSPC'''
*** '''ARCHES: M1 CSPC'''
* '''<span style="color:#ff0000">Apalutamide</span>'''
** '''<span style="color:#ff0000">MOA: binds directly to the</span>''' ligand-binding domain of '''the androgen receptor''' and prevents androgen-receptor translocation, DNA binding, and androgen-receptor–mediated transcription
** '''<span style="color:#ff0000">Contraindications</span>'''
***'''<span style="color:#ff0000">History of seizures</span>'''
**'''<span style="color:#ff0000">Adverse events (first 6 same as enzalutamide):</span>'''
**# '''<span style="color:#ff0000">HTN</span>'''
**# '''<span style="color:#ff0000">Diarrhea</span>'''
**# '''<span style="color:#ff0000">Fatigue</span>'''
**# '''<span style="color:#ff0000">Seizures</span>'''
**#* '''<1% of patients in clinical trials'''
**# '''<span style="color:#ff0000">Falls</span>'''
**# '''<span style="color:#ff0000">Fracture</span>'''
**# '''<span style="color:#ff0000">Hypothyroidism</span>'''
**# '''Rash'''
**# '''Increased cholesterol'''
**# '''Anemia'''
**# '''Hyperglycemia'''
**# '''Nausea'''
**# '''Weight loss'''
**# '''Arthralgia'''
** '''Recommended monitoring (as per Cancer Care Ontario)'''
*** '''TSH: baseline and as clinically indicated'''
*** '''ECG: baseline and as clinically indicated; more frequent in patients at risk of QTc prolongation'''
*** '''INR: if warfarin cannot be discontinued; baseline and during apalutamide treatment'''
*** '''Clinical assessment of adverse events: at each visit'''
** '''Trials with apalutamide'''
*** '''SPARTAN: MO CRPC'''
*** '''TITAN: M1 CSPC'''
* '''<span style="color:#ff0000">Darolutamide</span>'''
** '''<span style="color:#ff0000">Low penetration of the blood–brain barrier and low binding affinity for γ-aminobutyric acid type A receptors</span>'''
** '''Advantage:'''
**# '''Fewer and less severe toxic effects than apalutamide and enzalutamide'''
** '''Trials with darolutamide'''
*** '''ARAMIS: M0 CRPC'''