{"key":"Abiraterone mCRPC","text":"Abiraterone for mCRPC","info":"\n <strong>Abiraterone acetate (Zytiga®)</strong> is a selective, irreversible CYP17 inhibitor used in combination with prednisone for treating <strong>metastatic castration-resistant prostate cancer (mCRPC)</strong>.\n <br><br>\n It blocks androgen biosynthesis, prolongs survival, and improves symptoms in both pre- and post-chemotherapy settings. It is now <strong>PHARMAC-funded in New Zealand</strong> under Special Authority.\n ","children":[{"key":"Context","text":"Prostate Cancer Burden","info":"\n Prostate cancer is one of the most common cancers globally, accounting for 8% of diagnoses and deaths (2012).\n <br><br>\n <strong>Economic burden:</strong><br>\n - Lifetime cost per US patient: >$110,000<br>\n - US-wide 2008 cohort: $12.4 billion<br><br>\n <strong>Progression Model:</strong><br>\n Localised → Rising PSA → Metastases → CRPC → Death\n ","children":[{"key":"DetectionStats","text":"Disease Progression Stats","info":"\n - 10–20% of men present with metastatic disease<br>\n - 20–30% of localised cases eventually metastasise<br>\n - Median survival for mCRPC used to be <2 years\n "}]},{"key":"TherapyEvolution","text":"Treatment Evolution","info":"\n <strong>Before 2004:</strong> Only ADT, palliative intent<br>\n <strong>2004:</strong> Docetaxel + prednisone shows ~2-month OS benefit<br>\n <strong>Post-2010:</strong> New agents target androgen axis (e.g. abiraterone)\n ","children":[{"key":"AbirateroneDesign","text":"Abiraterone Mechanism","info":"\n Abiraterone inhibits CYP17 enzymes (17α-hydroxylase and C17,20-lyase), blocking androgen synthesis in the adrenal glands and tumor microenvironment.\n <br><br>\n Leads to ↓ testosterone and ↑ mineralocorticoids → side effects like hypertension, hypokalaemia, oedema.<br>\n Requires co-treatment with low-dose prednisone.\n "},{"key":"Comparison","text":"Comparison to Ketoconazole","info":"\n Ketoconazole was a non-specific CYP17 inhibitor with high toxicity.<br>\n Abiraterone is more potent and selective with a better safety profile.\n "}]},{"key":"NZContext","text":"New Zealand Use","info":"\n <strong>Findings:</strong><br>\n - ADT underused; chemotherapy rarely administered<br>\n - Māori/Pacific men more likely to receive ADT/orchidectomy<br>\n - Monitoring (e.g. PSA) not always consistent<br><br>\n <strong>PHARMAC Funding (May 2015):</strong><br>\n Abiraterone listed under Special Authority for mCRPC, pre- or post-chemotherapy\n ","children":[{"key":"Criteria","text":"Eligibility Criteria","info":"\n <strong>Initial:</strong> mCRPC with metastases, ECOG 0–1 (or 0–2 post-taxane), progression after ADT<br>\n <strong>Renewal:</strong> PSA response, no clinical progression, no taxane use, ongoing benefit\n "}]},{"key":"TrialEvidence","text":"Clinical Trials","info":"\n Two key Phase III trials demonstrate survival and quality-of-life benefits of abiraterone + prednisone in mCRPC.\n ","children":[{"key":"COUAA301","text":"Post-Chemo (COU-AA-301)","info":"\n <strong>Participants:</strong> 1195 men with prior docetaxel<br>\n <strong>Results:</strong> OS 14.8 vs 10.9 months; rPFS, PSA response improved<br>\n <strong>AEs:</strong> Mostly mild, mineralocorticoid-related\n "},{"key":"ElderlySubgroup","text":"Elderly (≥75) Subgroup","info":"\n <strong>OS:</strong> 15.6 vs 9.3 months<br>\n <strong>PSA Response:</strong> 34% vs 8%<br>\n Well-tolerated in older patients\n "},{"key":"COUAA302","text":"Pre-Chemo (COU-AA-302)","info":"\n <strong>Participants:</strong> 1088 chemo-naïve men<br>\n <strong>rPFS:</strong> 16.5 vs 8.3 months<br>\n <strong>OS:</strong> 34.7 vs 30.3 months (adjusted)<br>\n <strong>Other Benefits:</strong> Delayed chemo, less opiate use, better quality of life\n "},{"key":"EAP","text":"Real-World (EAP Study)","info":"\n <strong>Sample:</strong> 2314 men post-chemo (23 countries)<br>\n <strong>Median follow-up:</strong> 5.7 months<br>\n <strong>Findings:</strong> No new safety signals; AE profile similar to COU-AA-301\n "}]},{"key":"Conclusion","text":"Concluding Remarks","info":"\n - Abiraterone confirms importance of androgen inhibition in mCRPC<br>\n - Part of a growing treatment arsenal (e.g. enzalutamide, sipuleucel-T)<br>\n - No biomarker exists to choose agent order<br>\n - Early treatment, monitoring, and multidisciplinary care improve outcomes\n "}]}