Department of Medical Oncology.
Clinical Epidemiology and Trials Organization Unit.
Ann Oncol. 2015 Jan;26(1):167-172. doi: 10.1093/annonc/mdu485. Epub 2014 Oct 24.
In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB).
Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%.
From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded.
The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.
20 世纪 90 年代末，大剂量化疗（HDCT）和干细胞挽救治疗对晚期和预后不良的生殖细胞瘤（GCT）患者有一定效果。我们开始了一项随机 II 期试验，以评估与顺铂、依托泊苷和博来霉素（PEB）相比，序贯 HDCT 的疗效。
患者被随机分配接受每 3 周 4 个周期的 PEB 或 2 个周期的 PEB 后进行高强度方案（HDS），包括 HD 环磷酰胺（7.0 g/m2）、2 个周期的顺铂和 HD 依托泊苷（2.4 g/m2），并进行干细胞支持，以及 1 个周期的 HD 卡铂[曲线下面积（AUC）27 mg/ml×min]联合自体干细胞移植。在两个治疗组中，在有残留疾病的情况下，计划进行化疗后手术。主要终点是无进展生存期（PFS）。该研究旨在检测 5 年 PFS（从 40%提高至 70%）提高 30%的疗效，双侧α为 5%，把握度为 80%。
1996 年 12 月至 2007 年 3 月，共 85 例患者被随机分配：PEB 组 43 例，HDS 组 42 例。中位随访时间为 114.2 个月（四分位距[IQR]：87.7-165.8）。28 例（65.1%）和 29 例（69.1%）患者获得完全或部分缓解且标志物正常（PRm-）。PEB 和 HDS 组的 5 年 PFS 分别为 55.8%（95% CI：42.8-72.8）和 54.8%（95% CI：41.6%-72.1%）（对数秩检验 P = 0.726）。5 年总生存率分别为 62.8%（95% CI：49.9-79.0）和 59.3%（95% CI：46.1-76.3）。PEB 组发生 1 例治疗相关死亡。
该研究未达到主要终点。此外，高于预期的常规剂量化疗的生存估计应被考虑在内，这可能限制了一线治疗的进一步改善。临床试验.gov：NCT02161692。
