治疗转移性去势抵抗性前列腺癌（mCRPC）通过新药物组合来改善临床结果具有挑战性。临床前研究表明，卡巴嗪酯与多环花青素相比具有更优异的抗肿瘤效果。基因表达谱分析显示这些紫杉醇对细胞周期中的细胞产生不同效果。mCRPC由于缺乏RB基因，使得其对紫杉醇过敏。这些数据提示，卡巴嗪酯与阿比特龙联合治疗可能会影响治疗反应。我们设计了一个随机非比较的II期试验，比较了使用阿比特龙醋酸盐/泼尼松和使用阿比特龙醋酸盐/泼尼松加卡巴嗪酯（AAP + C）治疗mCRPC的效果。在这个包括81名mCRPC男性的试验中，我们评估了这两种治疗方案的放射图像进展无进展生存期（rPFS）、前列腺特异抗原（PSA）进展无进展生存期、总体客观反应和安全性。将患者根据Halabi法则分为高风险组和低风险组。我们还进行实时评估RB状态和循环肿瘤细胞（CTC）分析，以与临床结果相关联。这两个治疗阶段均有良好耐受性。AAP组的中位rPFS为6.4个月（95% CI，3.8至10.6），中位总生存期为18.3个月（95% CI，14.4至37.6）。有56%的患者PSA值下降≥50%。AAP + C组的中位rPFS为14.8个月（95% CI，10.6至16.4），中位总生存期为24.5个月（95% CI，20.4至35.0）。有92.1%的患者PSA值下降≥50%。从术前肿瘤活检中的RB表达、循环肿瘤细胞或组织外植物中无法识别出可能从AAP + C中受益的人群。AAP + C具有安全性、rPFS和OS持续时间改善以及更高比例的PSA下降。这表明与顺序使用相比，提前使用AAP + C可能会使某些人受益。还需要进一步研究来识别这一人群。

Improving clinical outcomes with novel drug combinations to treat metastatic castration-resistant prostate cancer (mCRPC) is challenging. Preclinical studies showed cabazitaxel had superior antitumor efficacy compared with docetaxel. Gene expression profiling revealed divergent effects of these taxanes in cycling cells. mCRPC are RB deficient rendering them hypersensitive to taxanes. These data suggested that upfront treatment with cabazitaxel with abiraterone may affect therapeutic response. We designed a phase II randomized noncomparative trial of abiraterone acetate/prednisone (AAP) or AAP and cabazitaxel (AAP + C) in men with mCRPC to address this hypothesis.This trial of 81 men with mCRPC determined the radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) progression-free survival, overall objective response, and safety of AAP or AAP + C. Equally allocated patients received AAP followed by switching to cabazitaxel upon radiographic progression (arm 1) or upfront with AAP + C (arm 2). Patients were stratified into high-/low-risk groups by the Halabi nomogram. Real-time assessment of RB status and circulating tumor cell (CTC) analysis to correlate with clinical outcomes was exploratory.Both treatment arms were well-tolerated. Median rPFS in AAP was 6.4 months (95% CI, 3.8 to 10.6) and median overall survival (OS) 18.3 months (95% CI, 14.4 to 37.6), respectively. Fifty-six percent of patients showed ≥50% decline in PSA. Median rPFS in AAP + C was 14.8 months (95% CI, 10.6 to 16.4), and median OS 24.5 months (95% CI, 20.4 to 35.0). There was a ≥50% decline in PSA in 92.1% of men. Neither RB expression in pretherapy tumor biopsy, CTC, or tissue explants identified those who may benefit from AAP + C.AAP + C was safe with improved rPFS, OS duration, and a higher proportion of PSA declines. This suggests that AAP + C given earlier rather than sequentially may benefit some men. Further work is needed to identify this population.