Department of Urology, Sapporo Medical University School of Medicine, Sapporo
Department of Urology, Sapporo Medical University School of Medicine, Sapporo.
Ann Oncol. 2014 Jun;25(6):1192-8. doi: 10.1093/annonc/mdu126. Epub 2014 Mar 24.
This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy.
Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm.
Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC.
This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment.
C000000093.
本研究旨在确定新辅助甲氨蝶呤、多柔比星、长春碱和顺铂（MVAC）在接受根治性膀胱切除术的肌层浸润性膀胱癌（MIBC）患者中的临床获益。
MIBC（T2-4aN0M0）患者被随机分配接受两个周期的新辅助 MVAC 治疗，然后进行根治性膀胱切除术（NAC 组）或单独进行根治性膀胱切除术（RC 组）。主要终点是总生存期（OS）。次要终点是无进展生存期、手术相关并发症、化疗期间的不良事件、膀胱切除术标本中无残余肿瘤的比例以及生活质量。为了检测 NAC 组 5 年 OS 从 RC 组的 45%提高到 57%，需要 80%的效能，每个臂需要 176 个事件。
共 130 名患者被随机分配到 RC 组（n=66）和 NAC 组（n=64）。由于入组缓慢，在最初计划的患者数量达到之前，患者登记就已经终止了。在第二次中期分析中，在提前停止患者入组后不久，数据和安全监测委员会建议提前公布结果，因为该试验没有足够的能力得出明确的结论。尽管 NAC 组的 OS 优于 RC 组，但差异无统计学意义[风险比 0.65，多重调整后 99.99%置信区间 0.19-2.18，单侧 P=0.07]。在 NAC 组和 RC 组中，分别有 34%和 9%的患者 pT0（P<0.01）。在亚组分析中，几乎所有亚组的 OS 均有利于 NAC。
本试验显示，接受新辅助 MVAC 的患者 pT0 比例显著增加，OS 较好。MVAC 的 NAC 仍然可以被认为是一种有前途的标准治疗方法。
UMIN 临床试验注册标识符：C000000093。
