Atalan Hejar, Morgan Michael A, Ivanyi Philipp, Kappler Paula, Heidel Florian H, Reuter Christoph W M
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Institute of Experimental Hematology, Hannover Medical School, Carl- Neuberg-Str. 1, 30625, Hannover, Germany.
Sci Rep. 2025 Jun 20;15(1):20130. doi: 10.1038/s41598-025-04667-0.
Docetaxel resistance, particularly post-androgen-receptor targeted therapy (ART), undermines its clinical utility in metastatic castration-resistant prostate cancer (mCRPC). This study explores the impact of docetaxel plus carboplatin (DC) chemotherapy on serum testosterone levels in metastatic docetaxel-resistant prostate cancer (mDRPC) patients. 123 mDRPC patients were categorized into three groups: (1) no previous ART (n = 65), (2) previous ART with serum free testosterone (FT) > detection limit (DL) at baseline (n = 31), and (3) previous ART with FT < DL at baseline (n = 27). Salvage DC chemotherapy led to significant reductions in FT and total testosterone (TT) levels in groups 1 and 2 (p < 0.05). Group 1 saw FT decrease from 0.85 pg/mL to below the DL (< 0.18 pg/mL) with 54.3% achieving complete reduction (CR); group 2 showed FT decrease from 0.28 pg/mL to below the DL with 67.7% achieving CR; group 3 had baseline FT values already below the DL with 96.3% maintaining this level. TT reductions to below the DL occurred in all groups. Low FT was an independent predictor for better PFS and for improved OS in groups 1 and 2. Our data indicate that adding carboplatin may improve the therapeutic effects of docetaxel in a castration-dependent setting.
多西他赛耐药，尤其是在雄激素受体靶向治疗（ART）后出现的耐药，削弱了其在转移性去势抵抗性前列腺癌（mCRPC）中的临床应用价值。本研究探讨了多西他赛联合卡铂（DC）化疗对转移性多西他赛耐药前列腺癌（mDRPC）患者血清睾酮水平的影响。123例mDRPC患者被分为三组：（1）既往未接受ART治疗（n = 65），（2）既往接受ART治疗且基线时血清游离睾酮（FT）>检测限（DL）（n = 31），（3）既往接受ART治疗且基线时FT<DL（n = 27）。挽救性DC化疗导致第1组和第2组患者FT和总睾酮（TT）水平显著降低（p<0.05）。第1组中，FT从0.85 pg/mL降至DL以下（<0.18 pg/mL）,54.3%的患者实现完全降低（CR）；第2组中，FT从0.28 pg/mL降至DL以下，67.7%的患者实现CR；第3组基线FT值已低于DL，96.3%的患者维持该水平。所有组的TT均降至DL以下。低FT是第1组和第2组患者无进展生存期（PFS）延长和总生存期（OS）改善的独立预测因素。我们的数据表明，在去势依赖的情况下，加用卡铂可能会提高多西他赛的治疗效果。
