Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Cancer. 2013 Oct 15;119(20):3610-8. doi: 10.1002/cncr.28270. Epub 2013 Aug 13.
The current trial evaluated 2 common therapies for patients with advanced prostate cancer, docetaxel and hormonal therapy (HT), in the surgical adjuvant setting.
TAX-3501 was a randomized, phase 3, adjuvant study post-radical prostatectomy (RP) in high-risk patients with prostate cancer (n=228) comparing 18 months of HT with (CHT) without docetaxel chemotherapy either immediately (I) or deferred (D). High-risk disease was defined as a 5-year freedom-from-disease-progression rate of ≤ 60% as predicted by a post-RP nomogram. Progression-free survival (PFS), including prostate-specific antigen disease recurrence, was the primary endpoint. The authors also assessed the accuracy of the nomogram and analyzed testosterone recovery in 108 patients treated with HT who had at least 1 posttreatment testosterone value.
Between December 2005 and September 2007, 228 patients were randomized between the treatment cohorts. TAX-3501 was terminated prematurely because of enrollment challenges, leaving it underpowered to detect differences in PFS. After a median follow-up of 3.4 years (interquartile range, 2.3-3.8 years), 39 of 228 patients (17%) demonstrated PSA disease progression, and metastatic disease progression occurred in 1 patient. The median time to baseline testosterone recovery after the completion of treatment was prolonged at 487 days (95% confidence interval, 457-546 days). The nomogram's predicted versus observed freedom from disease progression was significantly different for the combination D(HT) and D(CHT) group (P<.00001).
TAX-3501 illustrated several difficulties involved in conducting postoperative adjuvant systemic trials in men with high-risk prostate cancer: the lack of consensus regarding patient selection and treatment, the need for long follow-up time, nonvalidated intermediate endpoints, evolving standard approaches, and the need for long-term research support. Except for selected patients at very high-risk of disease recurrence and death, surgical adjuvant trials in patients with prostate cancer may not be feasible.
本研究评估了晚期前列腺癌患者的两种常用疗法，即多西他赛和激素治疗（HT），并将其应用于手术辅助治疗。
TAX-3501 是一项随机、III 期、辅助性研究，纳入了 228 例根治性前列腺切除术（RP）后高危前列腺癌患者，比较了 18 个月的 HT 联合（CHT）或不联合多西他赛化疗（立即[I]或延迟[D]）的疗效。高危疾病定义为基于 RP 列线图预测的 5 年无疾病进展率（FFDP）≤60%。无进展生存期（PFS），包括前列腺特异性抗原（PSA）疾病复发，是主要终点。作者还评估了列线图的准确性，并分析了至少有 1 次治疗后睾酮值的 108 例接受 HT 治疗患者的睾酮恢复情况。
2005 年 12 月至 2007 年 9 月，228 例患者被随机分为治疗组。由于入组困难，TAX-3501 提前终止，使该研究无法检测 PFS 的差异。中位随访 3.4 年（四分位间距 2.3-3.8 年）后，228 例患者中有 39 例（17%）出现 PSA 疾病进展，1 例发生远处转移。治疗结束后，基线睾酮恢复的中位时间延长至 487 天（95%置信区间 457-546 天）。列线图预测的无疾病进展率与组合 D（HT）和 D（CHT）组的实际观察结果有显著差异（P＜0.00001）。
TAX-3501 研究说明了在高危前列腺癌男性中进行术后辅助全身治疗临床试验所面临的几个困难：患者选择和治疗方法缺乏共识，需要长期随访，缺乏中间终点验证，标准治疗方法不断演变，以及需要长期的研究支持。除了疾病复发和死亡风险极高的特定患者外，前列腺癌患者的手术辅助试验可能不可行。
