Medical Oncology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Medical Oncology Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
Int J Radiat Oncol Biol Phys. 2019 Feb 1;103(2):344-352. doi: 10.1016/j.ijrobp.2018.10.005. Epub 2018 Oct 12.
Docetaxel improves survival in patients with metastatic prostate cancer. This randomized phase 2 trial aimed to assess the activity of weekly docetaxel with radiation therapy (RT) plus androgen deprivation in patients with high-risk localized prostate cancer. The study examined the benefit of 9 weekly docetaxel administrations to RT plus 3 years of luteinizing hormone-releasing hormone analogues.
A total of 132 patients were recruited for the study. Patients' characteristics included T3-T4 stage (81.1%), Gleason score ≥8 (77.3%), prostate-specific antigen level >20 ng/mL (28.9%), and pN+ (18.2%). All patients included in the trial received either the standard-of-care control arm with luteinizing hormone-releasing hormone analogues plus RT (arm A) or the experimental arm (RT + 9 weekly cycles of docetaxel + 3 years of androgen deprivation therapy, arm B). The primary objective was to achieve a high percentage of patients who were free of biochemical recurrence within 5 years of randomization. Secondary endpoints included biochemical recurrence-free survival (BRFS), progression-free survival (PFS), overall survival (OS), clinical response rate, biochemical response rate, and toxicity.
No difference between the arms of the study was found in biochemical recurrence (93.4% at 60 months for arm A vs 85.3% for arm B; P = .3297). PFS at 60 months was 93.4% and 83.7% in arms A and B, respectively (P = .2532). Five-year survival was 93.3% (95% confidence interval, 83.1-97.45) in arm A versus 93.6% (83.8-97.55) in arm B; median PFS and OS have not been reached. Prostate-specific antigen level ≤0.2 ng/mL at 3 months after the end of treatment was seen in 81.25% of patients in arm A compared with 90.48% of patients in arm B (P = .2028). BRFS was not significantly different between treatment arms. Diarrhea was the main nonhematologic toxicity. Long-term follow-up has not yet been enough to meet median PFS and OS.
Concurrent weekly docetaxel can be administered safely with standard doses of RT without a significant increase in the toxicity profile. No statistically significant differences for 5-year BRFS, PFS, and OS have been observed when docetaxel was added to conventional treatment.
多西他赛可提高转移性前列腺癌患者的生存率。本随机 2 期试验旨在评估高危局限性前列腺癌患者每周多西他赛联合放射治疗（RT）加雄激素剥夺治疗的疗效。该研究考察了在 RT 基础上加用 9 个周期每周多西他赛联合 3 年促黄体激素释放激素类似物治疗的获益。
共有 132 例患者入组该研究。患者特征包括 T3-T4 期（81.1%）、Gleason 评分≥8（77.3%）、前列腺特异性抗原（PSA）水平>20ng/mL（28.9%）和 pN+（18.2%）。所有入组患者均接受标准治疗（黄体生成素释放激素类似物加 RT，A 组）或试验组（RT+9 个周期每周多西他赛+3 年雄激素剥夺治疗，B 组）。主要终点是在随机分组后 5 年内实现较高比例的生化无复发生存率。次要终点包括生化无复发生存（BRFS）、无进展生存（PFS）、总生存（OS）、临床缓解率、生化缓解率和毒性。
研究组之间的生化复发率无差异（A 组为 60 个月时 93.4%，B 组为 85.3%；P=0.3297）。60 个月时 PFS 分别为 A 组 93.4%和 B 组 83.7%（P=0.2532）。A 组 5 年生存率为 93.3%（95%置信区间，83.1-97.45），B 组为 93.6%（83.8-97.55）；中位 PFS 和 OS 尚未达到。A 组有 81.25%的患者在治疗结束后 3 个月时 PSA 水平≤0.2ng/mL，B 组有 90.48%的患者（P=0.2028）。BRFS 在治疗组之间无显著差异。腹泻是主要的非血液学毒性。长期随访尚未足以达到中位 PFS 和 OS。
每周多西他赛联合标准剂量 RT 治疗可安全进行，且毒性谱无显著增加。当多西他赛联合常规治疗时，5 年 BRFS、PFS 和 OS 无统计学显著差异。
