Platinum-based chemotherapy for variant castration-resistant prostate cancer (aggressive variant criteria)
This trial defined clinical criteria for aggressive variant prostate cancer, such as visceral spread, low PSA relative to tumour burden and neuroendocrine features, and showed that these men respond to carboplatin-docetaxel followed by etoposide-cisplatin.
Overview
Phase 2 study of 120 men with castration-resistant prostate cancer meeting proposed anaplastic (aggressive variant) criteria treated with first-line carboplatin and docetaxel followed at progression by etoposide and cisplatin.
Response to first-line therapy occurred in the majority, median overall survival was 16 months, and the clinical criteria identified a group behaving like small-cell carcinoma even when histology showed adenocarcinoma.
- Aggressive variant criteria defined: visceral metastases, lytic bone metastases, bulky nodes, low PSA relative to burden, neuroendocrine markers, short response to hormonal therapy.
- Median overall survival 16 months with platinum-based sequential therapy.
The aggressive variant criteria are used to select men for platinum-based chemotherapy without needing neuroendocrine histology, and underpin trials of platinum combinations and PARP inhibitors in this group.
- Single-arm phase 2; criteria were subsequently linked to combined RB1, TP53 and PTEN loss.