Adra Nabil, Abonour Rafat, Althouse Sandra K, Albany Costantine, Hanna Nasser H, Einhorn Lawrence H
All authors: Indiana University School of Medicine, Indianapolis, IN.
J Clin Oncol. 2017 Apr 1;35(10):1096-1102. doi: 10.1200/JCO.2016.69.5395. Epub 2016 Nov 21.
Purpose Patients with relapsed metastatic germ cell tumor (GCT) can be cured with second-line and even third-line regimens. We report survival outcomes of patients treated with high-dose chemotherapy (HDCT) and peripheral-blood stem-cell transplantation (PBSCT) at Indiana University between 2004 and 2014. Patients and Methods We conducted a retrospective analysis of 364 consecutive patients with GCT who progressed after cisplatin-based combination chemotherapy and were subsequently treated with HDCT and PBSCT. Three hundred forty-one patients received two consecutive courses of HDCT consisting of 700 mg/m carboplatin and 750 mg/m etoposide, each for 3 consecutive days, and each followed by PBSCT. Twenty-three patients received only a single course of HDCT because of progressive disease or toxicity. Cox proportional hazards models were used to test predictors of disease progression. Results The median age was 32 years (range, 17 to 70 years). With a median follow-up of 3.3 years, the 2-year progression-free survival (PFS) was 60% (95% CI, 55% to 65%) and the 2-year overall survival was 66% (95% CI, 60% to 70%). Three hundred three patients received HDCT as second-line therapy with a 2-year PFS of 63% (95% CI, 57% to 68%), and 61 patients received HDCT as third-line or later therapy with a 2-year PFS of 49% (95% CI, 36% to 61%). In a multivariable analysis, factors associated with disease progression included use of HDCT as third-line or later therapy, platinum-refractory disease, mediastinal primary tumor site, nonseminoma histology, intermediate- or poor-risk disease at the time of GCT diagnosis, and human chorionic gonadotropin ≥ 1,000 mIU/mL at initiation of HDCT. There were nine treatment-related deaths. Secondary leukemia developed in five patients. Conclusion This large single-institution study demonstrates that patients with relapsed metastatic GCT are curable by HDCT plus PBSCT even when used in third-line or later therapy.
目的 复发转移性生殖细胞肿瘤（GCT）患者可通过二线甚至三线治疗方案治愈。我们报告了2004年至2014年间在印第安纳大学接受高剂量化疗（HDCT）和外周血干细胞移植（PBSCT）治疗的患者的生存结果。患者与方法 我们对364例连续的GCT患者进行了回顾性分析，这些患者在基于顺铂的联合化疗后病情进展，随后接受了HDCT和PBSCT治疗。341例患者接受了连续两个疗程的HDCT，包括700mg/m²卡铂和750mg/m²依托泊苷，各连续使用3天，每次之后均进行PBSCT。23例患者因疾病进展或毒性仅接受了一个疗程的HDCT。使用Cox比例风险模型来测试疾病进展的预测因素。结果 中位年龄为32岁（范围17至70岁）。中位随访3.3年，2年无进展生存率（PFS）为60%（95%CI，55%至65%），2年总生存率为66%（95%CI，60%至70%）。303例患者接受HDCT作为二线治疗，2年PFS为63%（95%CI，57%至68%），61例患者接受HDCT作为三线或更晚治疗，2年PFS为49%（95%CI，36%至61%）。在多变量分析中，与疾病进展相关的因素包括使用HDCT作为三线或更晚治疗、铂难治性疾病、纵隔原发性肿瘤部位、非精原细胞瘤组织学、GCT诊断时的中危或低危疾病，以及HDCT开始时人绒毛膜促性腺激素≥1000mIU/mL。有9例治疗相关死亡。5例患者发生了继发性白血病。结论 这项大型单机构研究表明，复发转移性GCT患者即使在三线或更晚治疗中使用HDCT加PBSCT也可治愈。
