一项多中心 TAXIF II 研究：在顺铂为基础的化疗失败的生殖细胞肿瘤（GCT）患者中，采用大剂量化疗（HDCT）联合造血干细胞移植（HSCT）的 II 期临床试验。
A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.
机构信息
Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris.
Department of Medicine, Institut Gustave Roussy, Villejuif.
出版信息
Ann Oncol. 2014 Sep;25(9):1775-1782. doi: 10.1093/annonc/mdu198. Epub 2014 Jun 3.
BACKGROUND
High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT.
PATIENTS AND METHODS
This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate.
RESULTS
Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81).
CONCLUSION
The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens.
TRIAL REGISTRATION NUMBER
NCT00231582.
背景
大剂量化疗（HDCT）是治疗生殖细胞瘤（GCT）患者的有效挽救治疗方法。在首次挽救治疗中，30%-70%的患者可能获得持久缓解。即使在 HDCT 作为后续挽救治疗时，仍有多达 20%的患者可能被治愈。然而，患有难治性/复发性疾病的患者仍有非常差的长期预后，需要更早地进行 HDCT 干预。
患者和方法
这项 II 期试验针对的是接受基于顺铂的化疗后复发的非难治性患者。纳入标准包括二线化疗后复发的精原细胞瘤、一线或二线化疗后复发的非精原细胞瘤、一线治疗后部分缓解、首次复发的原发性纵隔 GCT。患者接受两个周期的表柔比星和紫杉醇（Epi-Tax）联合治疗，然后进行三个连续的 HDCT，一个使用紫杉醇/噻替哌（Thio-Tax）联合治疗，两个使用 5 天异环磷酰胺-卡铂-依托泊苷方案。主要目标是确定完全缓解率。
结果
2004 年 9 月至 2007 年 12 月期间，共纳入 45 例患者：44 例接受了第一个 HDCT 周期，39 例接受了两个 HDCT 周期，29 例能够接受整个方案。16 例患者未接受整个方案，包括 8 例（17.7%）因毒性副作用。有 2 例患者（4.4%）死于毒性反应，17 例（37.7%）死于疾病进展。中位随访时间为 26 个月（范围为 4-51 个月），在意向治疗分析中，最终总缓解率为 48.8%（包括完全缓解率 15.5%和部分缓解/阴性血清标志物率 26.6%）。中位无进展生存期（PFS）和总生存期（OS）分别为 22 个月[95%置信区间（CI）2-未达到]和 32 个月（95%CI 4-49）。2 年 PFS 呈 50%（95%CI 32-67）平台设置，2 年 OS 为 66%（95%CI 44-81）。
结论
TAXIF II 方案对接受基于顺铂的化疗后复发的非难治性 GCT 患者有效。在 HDCT 方案领域，毒性死亡率仍然可以接受。
试验注册号
NCT00231582。
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