Editing Castrate-Resistant Prostate Cancer (section)

===== Options (3): =====

# Mitoxantrone (historical)
# Docetaxel
# Cabazitaxel

====== Mitoxantrone ======
* Historical
*First step forward in the chemotherapeutic management of CRPC; prednisone used prior
* 2 RCTs found that addition of mitoxantrone to either prednisone (Tannock et al, 1996) or hydrocortisone (Kantoff et al, 1999) resulted in significant improvements of various QOL parameters, including pain, but no difference in survival
* In 1997, FDA approved mitoxantrone with prednisone for patients with symptomatic CRPC
* Although it does not prolong survival, mitoxantrone has been approved to palliate symptoms associated with metastatic disease, and was often used in patients who have previously received docetaxel and/or cabazitaxel, or in those who would not tolerate these agents.[historical?]

====== Docetaxel ======
* The next significant advance in the use of chemotherapy for CRPC
* '''MOA: inhibits microtubule assembly and disassembly; member of the taxane family'''
* '''Standard first-line chemotherapy for mCRPC'''
** '''Prolongs progression-free and overall survival'''
** '''Reduces pain and improves quality of life'''
** '''TAX 327'''
*** Population: 1006 mCRPC patients with no previous chemotherapy treatment and stable pain scores
*** '''Randomized''' to (all with concomitant prednisone 5 mg twice daily) '''mitoxantrone vs. docetaxel 75 mg/m2 IV every 3 weeks vs. docetaxel 30 mg/m2''' IV weekly. All patients remained on ADT
*** '''Results:'''
**** Median follow-up: 20.7 months
**** '''OS significantly improved in the every-3-week docetaxel group, not in the weekly docetaxel group''' (18.9 months every 3 weeks, 17.3 months in the weekly docetaxel group, and 16.4 months in the mitoxantrone group)
* '''Adverse events (6):'''
*# '''Myelosuppression''' (neutropenia)
*# '''Fatigue'''
*# '''Fever'''
*# '''Diarrhea, abdominal pain, constipation'''
*# '''Peripheral edema'''
*# '''Neurotoxicity'''
*# '''Hyperlacrimation'''
*# '''Nail dystrophy'''

====== Cabazitaxel ======
* '''MOA: inhibits microtubule assembly and disassembly; member of the taxane family'''
* '''Indications'''
** '''mCRPC, post-docetaxel'''
* '''TROPIC trial'''
** '''Population:''' 755 '''patients with mCRPC who had progressed after docetaxel-based chemotherapy'''
** Randomized to mitoxantrone + prednisone vs. cabazitaxel + prednisone, each administered every 3 weeks
** Results:
*** Median follow-up: 12.8 months,
*** Cabazitaxel significantly improved OS by 2 months (median OS 15.1 months in the cabazitaxel arm compared to 12.7 months in men receiving mitoxantrone)
*** Cabazitaxel also improved PFS by 1.4 months (2.8 months cabazitaxel vs. 1.4 months mitoxantrone)
*** Cabazitaxel resulted in more-clinically-significant diarrhea, but its primary toxicity is hematologic with 82% of patients developing grade 3 or 4 neutropenia, 8% developing febrile neutropenia and 5% resulting in death. The FDA label indication for this drug recommends prophylactic neutrophil growth factor support in those patients most susceptible to neutropenia, including older individuals and those with significant prior radiotherapy.
** '''De Bono, Johann Sebastian, et al. "Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial." The Lancet 376.9747 (2010): 1147-1154.'''
* '''FDA-approved in 2010 for the second-line treatment of docetaxel-refractory mCRPC'''
* '''Adverse events'''
*# '''Neutropenia (including febrile neutropenia)'''
*# '''Diarrhea'''
** '''Use of growth factor support should be strongly considered when administering cabazitaxel'''

* Given the activity of cabazitaxel in docetaxel-pretreated patients, FIRSTANA assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC