Role and Dose of Prednisolone with Docetaxel and Cabazitaxel in CSPC and CRPC
Prednisolone Dosing with Docetaxel
For docetaxel chemotherapy in both CSPC and CRPC, the standard corticosteroid dose is prednisone 10 mg orally daily throughout treatment, based on the landmark TAX 327 trial that established docetaxel's survival benefit. 1
Docetaxel Regimens and Corticosteroid Use
In mCRPC: Docetaxel 75 mg/m² every 3 weeks with prednisone 10 mg daily is the FDA-approved standard regimen, demonstrating a median overall survival of 18.9 months versus 16.5 months with mitoxantrone (HR 0.79, p=0.009). 1
Alternative biweekly dosing: Docetaxel 50 mg/m² every 2 weeks with prednisone 10 mg daily showed improved survival (19.5 vs 17.0 months, p=0.015) and better tolerability with reduced febrile neutropenia (4% vs 14%) compared to the 3-weekly schedule. 1
In CSPC: When docetaxel is used upfront with ADT in castration-sensitive disease, the same prednisone 10 mg daily dosing applies throughout treatment. 1
Rationale for Corticosteroid Co-Administration
The corticosteroid serves multiple purposes: it provides anti-tumor activity through androgen axis suppression, reduces inflammatory side effects, and improves quality of life in symptomatic patients. 1
Prednisolone Dosing with Cabazitaxel
For cabazitaxel in mCRPC, prednisone or prednisolone 10 mg orally daily is mandatory throughout treatment and is part of the FDA-approved regimen, not optional. 1, 2, 3
Cabazitaxel Regimens and Corticosteroid Requirements
Standard dose: Cabazitaxel 20 mg/m² IV every 3 weeks with daily prednisone/prednisolone 10 mg is the recommended dose for most patients, based on the PROSELICA trial demonstrating non-inferiority to 25 mg/m² with improved safety (median OS 13.4 vs 14.5 months, HR 1.024). 2, 3
Higher dose option: Cabazitaxel 25 mg/m² every 3 weeks with daily prednisone/prednisolone 10 mg can be used in select healthier patients seeking more aggressive palliation, but requires primary prophylactic G-CSF in all patients at this dose. 2, 3
CARD trial regimen: The superior efficacy demonstrated in CARD (median OS 13.6 vs 11.0 months, HR 0.64, p=0.008) used cabazitaxel 25 mg/m² with prednisone/prednisolone 10 mg daily plus mandatory primary G-CSF prophylaxis in 92% of patients. 2, 3
Critical Safety Requirements with Cabazitaxel
Mandatory premedication: Before each cabazitaxel infusion, patients must receive IV antihistamine (diphenhydramine 25 mg or equivalent), corticosteroid (dexamethasone 8 mg or equivalent), and H2 antagonist to prevent hypersensitivity reactions. 2, 3
G-CSF prophylaxis: Primary prophylaxis with G-CSF is recommended for patients with high-risk clinical features and should be considered in all patients receiving 25 mg/m², given the 7.5% febrile neutropenia rate and 4.9% toxic death rate. 1, 2, 3
Antiemetic prophylaxis: Required before each infusion, can be given orally or intravenously. 3
Clinical Context: CSPC versus CRPC
In Castration-Sensitive Prostate Cancer (CSPC)
Docetaxel with prednisone 10 mg daily is used upfront with ADT in high-volume or high-risk metastatic disease, not cabazitaxel. 1
Cabazitaxel is not indicated in CSPC and should not be used in this setting despite showing activity in chemotherapy-naïve patients in the FIRSTANA trial. 2
In Castration-Resistant Prostate Cancer (CRPC)
First-line chemotherapy: Docetaxel 75 mg/m² every 3 weeks (or 50 mg/m² every 2 weeks) with prednisone 10 mg daily is the Category 1 preferred option for docetaxel-naïve mCRPC. 1
Post-docetaxel setting: Cabazitaxel with prednisone/prednisolone 10 mg daily is FDA-approved and NCCN Category 1 preferred specifically after progression on docetaxel, particularly in patients who have also failed a novel hormone therapy (abiraterone or enzalutamide). 1, 2
Common Pitfalls and Caveats
Corticosteroid Dosing Errors
Do not confuse abiraterone dosing: Abiraterone requires prednisone 5 mg twice daily (total 10 mg), while docetaxel and cabazitaxel use prednisone 10 mg once daily. 1
Do not omit daily corticosteroid: The daily prednisone/prednisolone is mandatory throughout cabazitaxel treatment and is part of the FDA-approved regimen, separate from the premedication corticosteroid. 2, 3
Neutropenia Management
Cabazitaxel carries significantly higher neutropenic risk than docetaxel (grade 3-4 neutropenia 41.8-73.3% vs 32%), requiring vigilant monitoring and prophylactic G-CSF, especially at the 25 mg/m² dose. 1, 2, 3
Febrile neutropenia with cabazitaxel (7-9%) necessitates dose reduction to one level lower and secondary G-CSF prophylaxis for all subsequent cycles. 3
Treatment Sequencing Considerations
Docetaxel rechallenge in mCRPC after prior docetaxel in CSPC is a Category 2A option (not Category 1), particularly in patients without definitive progression on prior docetaxel. 1
After progression on both docetaxel and a novel hormone therapy, cabazitaxel demonstrates superior outcomes compared to switching to an alternative hormone therapy (rPFS 8.0 vs 3.7 months, HR 0.54, p<0.0001). 2, 3