[ASCO2016]多西他赛能否改善高危前列腺癌患者生存？

背景：多西他赛已被证实可以延长晚期去势抵抗性前列腺癌患者的生存期，研究人员因此展开了该试验以评估6个疗程的多西他赛能否改善高危前列腺癌患者行根治性前列腺癌切除术后的无疾病生存期。

方法：459名患者被随机分配，A组接受6个疗程的多西他赛化疗，每3周75mg/m2；B组进行主动监测。首要重点是PSA升高值>0.5ng/ml。高危前列腺癌定义为pT2且切缘阳性的患者，Gleason评分4+3或更高，pT3b>GS 3+4。

结果：79.1%的患者进行完全部6个疗程的多西他赛治疗。首要终点出现前行挽救性放疗的患者，A组有8%，B组有10%。平均年龄62.2岁，平均基线PSA值为0.156，83.7%的患者为pT3且有37.5%的患者GS为8-10。在308名行淋巴结清扫术的患者中，55名（17.5%）出现远端转移。中位随访时间为56.8个月。A组中有43.2%的患者出现了研究终点，B组中有38.9%的患者出现了研究终点。在Kaplan-Meier分析中，两组BDFS曲线没有显著差异（p=0.078）。A组中有6名患者死亡，而B组只有3名。A组患者中有18.7%出现了粒细胞减少性发热。未出现与治疗相关的死亡。Cox回归模型的多变量分析显示，GS（p<0.001），pT分期（p=0.002）和切缘阳性（p=0.009）是疾病进程的重要预测因素。

结论：多西他赛在不进行化疗的情况下无法改善高危前列腺癌患者行根治性前列腺切除术后的BDFS。多西他赛单一疗法似乎会导致更快的生化进展。

摘要原文：

Background: Docetaxel has proved to prolong survival in advanced castrate resistant prostate cancer (PCa) and we therefore started this trial to evaluate if six courses of docetaxel improves biochemical disease free survival (BDFS) after radical prostatectomy for high risk PCa.

Methods: A total of 459 patients were randomised in 2005-2010 in this multinational openlabeled phase III study, to receive either 6 cycles of adjuvant docetaxel 75mg/m2 q 3 weeks (Arm A) or Surveillance (Arm B). Primary end-point was a rising PSA >0.5ng/ml. High risk prostate cancer was defined as pT2 with a positive margin if Gleasonscore (GS) 4+3 or higher, pT3b >GS 3+4, any lymph node positive disease with >GS 3+4, patients were followed for 5 years with PSA every 3 months. The study was powered to show a 15% difference at 5 years follow up.

Results: All six cycles were completed by 79.1% of the patients. Salvage radiotherapy before the primary end-point was reached was given to 8% in Arm A and 10% in Arm B. Mean age was 62.2 years, mean baseline PSA 0.156, 83.7% had pT3 disease and 37.5% had GS 8-10 at randomisation. Of the 308 patients that had a lymph node dissection, 55 (17.5%) had metastasis. Median follow up was 56.8 months. The endpoint was reached in 43.2% of patients; 47.9% in Arm A and 38.9% in Arm B. In a Kaplan-Meier analysis there was no significant difference between the BDFS curves (p=0.078), but the curve of Arm A crossed the curve of Arm B at 15 months and it was parallel at a 10% lower level beyond 24 months. There were 6 deaths from prostate cancer in Arm A and only 3 in Arm B. Febrile neutropenia occurred in 18.7% of the patients in Arm A. No deaths were related to treatment. In a Cox multivariate analysis excluding lymph node status, GS (p<0.001), pT-stage (p=0.002) and positive surgical margin (p=0.009) were significant predictors of progression while randomisation arm (p=0.09) did not reach significance.

Conclusions: Adjuvant docetaxel without hormonal therapy did not improve BDFS after radical prostatectomy for high risk prostate cancer. Instead, docetaxel as monotherapy seems to generate a more rapid biochemical progression in a subgroup of patients