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androgen-independent prostate cancer; castration resistant prostate cancer (CRPC)

Management: chemotherapy (androgen-independent metastatic disease) 1) docetaxel 36 mg/m2 IV weekly for 4 weeks, with or without calcitriol 45 mg PO 1 day prior to docetaxel [1] 2) docetaxel + prednisone every 3 weeks [2] 3) inhibition of CYP17 with abiraterone acetate +/-dexamethasone [3,4] is standard-of-care [8] - addition of the PARP inhibitor olaparib (Lynparza) to abiraterone (Zytiga) as initial treatment extends median progression-free survival [8] 4) addition of the PARP inhibitor talazoparib (Talzenna) to enzalutamide (Xtandi) significantly improved radiographic progression-free survival [9] 5) cabozantinib shows promise in clinical trial 6) no benefit of chemotherapy in addition to androgen deprivation prior to androgen-independence [5,6] 7) lutetium-177 PSMA-617 extends overall survival 15.3 vs 11.3 months vs standard therapy [7]

General

prostate cancer

References

  1. Beer TM et al, Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen- independent prostate cancer. A report from the ASCENT investigators. J Clin Oncol 2007, 25:669 PMID: 17308271
  2. Berthold DR et al, Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cance. Updated survival iin the TAX 327 study. J Clin Oncol 2008, 26:242 PMID: 18182665
  3. Attard G et al Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 2009 Aug 10; 27:3742. PMID: 19470933
  4. Reid AHM et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 2010 Feb 16; [e-pub ahead of print] Not yet indexed in PubMe http://dx.doi.org/10.1200/JCO.2009.24.6819
  5. Millikan RE et al Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol 2008 Dec 20; 26:5936. PMID: 19029421
  6. Gravis G et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): A randomised, open-label, phase 3 trial. Lancet Oncol 2013 Feb; 14:149 PMID: 23306100 - Sweeney C. Prostate cancer therapy: Going forwards by going backwards. Lancet Oncol 2013 Feb; 14:104. PMID: 23306099
  7. Ingram I Radioligand Therapy Boosts Survival in Metastatic CRPC. PSMA-directed agent improved overall survival by median 4 months. MedPage Today June 4, 2021 https://www.medpagetoday.com/meetingcoverage/asco/92931 - Morris MJ et al Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). American Society of Clinical Oncology (ASCO) 2021; Abstract LBA4.
  8. Kuznar W Add-On Olaparib Continues to Show Benefit in First-Line Treatment of mCRPC. Final PROpel analysis also shows trend toward overall survival improvement with PARP inhibitor. MedPage Today. Feb 17, 2013 https://www.medpagetoday.com/meetingcoverage/mgucs/103174
  9. Bassett M Adding Talazoparib to Enzalutamide Boosts PFS in Metastatic Prostate Cancer. Combination achieved a 37% reduction in risk of progression, death versus ARPI alone. MedPage Today February 17, 2023 https://www.medpagetoday.com/meetingcoverage/mgucs/103158