Current Trends in Chemotherapy in the Treatment of Metastatic Prostate Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Metastatic Castration-Resistant Prostate Cancer
2.1. Mitoxantrone
2.2. Docetaxel
2.3. Cabazitaxel
2.4. Combining Taxanes with Platinum Chemotherapy for mCRPC
3. Metastatic Castration-Sensitive Prostate Cancer
3.1. ADT Plus Docetaxel Doublet Therapy
3.2. Doublet Therapy (ADT Plus Docetaxel) in Low Versus High Volume mCSPC
3.3. ADT Plus Docetaxel and ARSI Therapy
3.4. ARSI Doublet Therapy Versus Triplet Therapy
4. Neuroendocrine Prostate Cancer
5. Role of Prednisone in Combination with Docetaxel
6. Financial Considerations in the Treatment of Prostate Cancer
7. Future Directions
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Clinical Trial Abbreviation | Full Clinical Trial Title |
---|---|
ARASENS [18] | A randomized, double-blind, placebo-controlled Phase III study of ODM-201 versus placebo in addition to standard androgen deprivation therapy and docetaxel in patients with metastatic hormone-sensitive prostate cancer |
CALGB 9182 [21] | Cancer and Leukemia Group-B 9182: hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer |
CARD [22] | A phase III, randomized, open label, multicenter study of Cabazitaxel versus an Androgen Receptor (AR)-targeted agent (abiraterone or enzalutamide) in mCRPC patients previously treated with Docetaxel and who rapidly failed a prior AR-targeted agent |
CHAARTED [23] | ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer |
DORA [24] | Phase 3 Trial of Docetaxel vs. Docetaxel and Radium-223 for Metastatic Castration-Resistant Prostate Cancer (mCRPC) |
ENZAMET [25] | Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer |
FIRSTANA [26] | Randomized, Open Label, Multi-Center Study comparing Cabazitaxel at 25 mg/m2 and at 20 mg/m2 in Combination with Prednisone Every 3 Weeks to Docetaxel in Combination with Prednisone in Patients with Metastatic Castration Resistant Prostate Cancer not Pretreated with Chemotherapy |
GETUG-AFU 15 [27] | Urogenital Tumor Study Group Association Française d’Urologie 15: Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer: a randomised, open-label, phase 3 trial |
PEACE-1 [19] | Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer: a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design |
ProBio [28] | A Biomarker Driven Study in Patients with Metastatic Prostate Cancer |
PROSELICA [15] | A Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in post-docetaxel patients with metastatic castration-resistant prostate cancer |
RECARDO [29] | A randomized phase II trial of docetaxel plus carboplatin versus docetaxel in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy |
STAMPEDE [30] | Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy |
TAX 327 [14] | Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer |
TROPIC [16] | Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial |
Tannock et al. [13] (N = 161) | CALGB 9182 [21] (N = 242) | TAX 327 [14] (N = 1006) | TROPIC [16] (N = 755) | PROSELICA [15] (N = 1200) | CARD [22] (N = 255) | FIRSTANA [26] (N = 1168) | |
---|---|---|---|---|---|---|---|
Treatment arms | Mitoxantrone plus prednisone vs. prednisone | Mitoxantrone plus hydrocortisone vs. hydrocortisone | Mitoxantrone vs. docetaxel 75 mg/m2 q3 weeks vs. docetaxel 30 mg/m2 weekly for 5/6 weeks | Cabazitaxel vs. mitoxantrone | Cabazitaxel 20 mg/m2 vs. 25 mg/m2 | Cabazitaxel vs. ARSI | Cabazitaxel 20 mg/m2 vs. 25 mg/m2 vs. docetaxel 75 mg/m2 |
Outcome measure | Palliative Response (29% vs. 12%) | Quality of life (improved with mitoxantrone) | OS | OS | OS | OS | OS |
HR | 0.76 (docetaxel q3 weeks compared to mitoxantrone) | 0.70 (cabazitaxel vs. mitoxantrone) | 1.024 (C20 vs. C25) | 0.64 (cabazitaxel vs. ARSI) | 0.97 (C25 vs. docetaxel) | ||
CI | 95% 0.62–0.94 | 95% 0.59–0.83 | One-sided 98.89% 1.184 | 95% 0.46–0.89 | 95% 0.82–1.16 | ||
p-value | 0.01 | 0.04 | 0.009 | <0.0001 | 0.008 | 0.757 | |
Median follow-up (months) | 20.8 | 12.8 | 9.2 |
GETUG-AFU 15 [27,39] (N = 385) | CHAARTED [23,38] (N = 790) | STAMPEDE [30,40] (N = 2962) 1 | |
---|---|---|---|
Number of cycles of docetaxel | 9 | 6 | 6 |
Gleason score 8 or higher (%) | 56.10 | 61.27 | 70.63 1 |
Median PSA level at start of ADT—ng/mL | |||
Docetaxel + ADT | 26.7 | 50.9 | 70 |
ADT | 25.8 | 52.1 | 67 |
Hazard ratio for death (ADT + docetaxel vs. ADT) | 0.88 | 0.72 | 0.81 |
95% CI | 0.68–1.14 | 0.59–0.89 | 0.69–0.95 |
p-value | 0.3 | 0.0018 | 0.009 |
Median follow-up (months) | 83.9 | 53.7 | 78.2 |
ARASENS [18,44] (N = 1306) | PEACE-1 [19] (N = 710) 1 | ENZAMET [25,45] (N = 503) 1 | |
---|---|---|---|
ARSI | Darolutamide | Abiraterone | Enzalutamide |
Number of cycles of docetaxel | 6 | 6 | 6 |
Gleason score 8 or higher (%) | 78.2 | 76.90 1 | 58.31 2 |
Hazard ratio for death | 0.68 (triplet vs. doublet therapy) | 0.75 (triplet vs. doublet therapy) | 0.82 (enzalutamide vs. standard non-steroidal anti-androgen) |
95% CI | 0.57–0.80 | 0.59–0.95 | 0.63–1.06 |
p-value | <0.001 | 0.017 | -- |
Median follow-up (months) | 43.7 | 52.8 | 68 2 |
mCSPC (for Fit Patients with High-Volume Disease) | mCRPC | Small Cell/Neuroendocrine Prostate Cancer |
---|---|---|
Docetaxel 75 mg/m2 every 3 weeks plus darolutamide, with or without daily prednisone Or Docetaxel 75 mg/m2 every 3 weeks plus abiraterone and daily prednisone | For patients with mCRPC who already received docetaxel for mCSPC but have not demonstrated definitive evidence of progression on prior docetaxel in the castration-sensitive setting, docetaxel rechallenge may be considered with: Docetaxel 75 mg/m2 every 3 weeks with concurrent steroids 2 | Cisplatin/etoposide Or Carboplatin/etoposide Or Docetaxel/carboplatin Or Cabazitaxel/carboplatin |
For patients who have not already received docetaxel in the castration-sensitive setting, docetaxel is usually preferred in the castration-resistant setting (prior to cabazitaxel): Docetaxel 75 mg/m2 every 3 weeks with concurrent steroids 2 | ||
If cancer progressed despite prior docetaxel, or patients intolerant of or unlikely to tolerate docetaxel: Cabazitaxel 20 or 25 mg/m2 every 3 weeks with concurrent steroids 2 | ||
For fit patients with aggressive variant prostate cancer, consider: Cabazitaxel 20 mg/m2 plus carboplatin AUC 4 mg/mL/min with concurrent steroids 2 |
ClinicalTrials.gov Identifier | Trial Name | Study Population | Study Objective | Study Arms | Outcome Measures |
---|---|---|---|---|---|
NCT03574571 [24] | DORA | Patients with mCRPC | Evaluate use of radium-223 along with docetaxel | Docetaxel 75 mg/m2 vs. docetaxel 60 mg/m2 + radium-223 | Primary: Overall survival Secondary: Radiographic progression-free survival Symptomatic Skeletal Event-free survival Time to total ALP progression On-treatment alterations in QOL |
NCT03903835 [28] | ProBio | Patients with mCRPC | Evaluate treatments based on biomarker signatures (inferred from diagnostic tissue or liquid biopsy) | Standard of care (with ARSIs, radium-223, cabazitaxel and docetaxel as possible options) vs. enzalutamide, abiraterone, carboplatin, cabazitaxel, docetaxel, or niraparib + abiraterone + prednisone depending on biomarker signature | Primary: Progression-free survival Secondary: Response rate Overall survival Quality of life Cost-effectiveness Safety and tolerability |
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Zhao, J.; Guercio, B.J.; Sahasrabudhe, D. Current Trends in Chemotherapy in the Treatment of Metastatic Prostate Cancer. Cancers 2023, 15, 3969. https://doi.org/10.3390/cancers15153969
Zhao J, Guercio BJ, Sahasrabudhe D. Current Trends in Chemotherapy in the Treatment of Metastatic Prostate Cancer. Cancers. 2023; 15(15):3969. https://doi.org/10.3390/cancers15153969
Chicago/Turabian StyleZhao, Janice, Brendan J. Guercio, and Deepak Sahasrabudhe. 2023. "Current Trends in Chemotherapy in the Treatment of Metastatic Prostate Cancer" Cancers 15, no. 15: 3969. https://doi.org/10.3390/cancers15153969
APA StyleZhao, J., Guercio, B. J., & Sahasrabudhe, D. (2023). Current Trends in Chemotherapy in the Treatment of Metastatic Prostate Cancer. Cancers, 15(15), 3969. https://doi.org/10.3390/cancers15153969