Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
J Clin Oncol. 2010 Apr 1;28(10):1706-13. doi: 10.1200/JCO.2009.25.1561. Epub 2010 Mar 1.
We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.
Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.
Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.
TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
我们之前报告了 TI-CE 方案（紫杉醇[T]加异环磷酰胺[I]，随后高剂量卡铂[C]加依托泊苷[E]，联合干细胞支持）在接受常规剂量挽救性治疗预后不良的生殖细胞瘤（GCT）患者中的剂量发现和 II 期试验。现在，我们报告了 TI-CE 在我们的 107 例患者的完整数据集的无病生存率（DFS）和总生存率（OS）的预测因素的疗效。
符合条件的患者患有进展性晚期 GCT，在接受化疗后出现疾病进展，并具有不良预后特征（性腺外原发部位、一线治疗不完全缓解[IR]或基于异环磷酰胺-顺铂的常规剂量挽救性治疗后复发/IR）。对预后因素进行了单变量和多变量分析（MVAs）。评估了 Einhorn 和 Beyer 预后模型的预测能力。
大多数患者对铂类药物有耐药性，并且对一线化疗有 IR。有 54 例（5%）完全缓解和 8 例（8%）部分缓解，且标志物阴性；5 年 DFS 为 47%，OS 为 52%（中位随访 61 个月）。两年后没有复发。21 例原发性纵隔非精原细胞瘤中，有 5 例（24%）持续无病。在 MVA 中，原发性纵隔部位（P<0.001）、两种或更多种先前治疗线（P<0.001）、基线人绒毛膜促性腺激素>或=1000 U/L（P=0.01）和肺转移（P=0.02）显著预测了不良的 DFS。根据 Beyer（P<0.002）和 Einhorn（P<0.05）模型，高危患者的预后均差于中危或低危患者。
TI-CE 是一种有效的 GCT 患者的挽救性治疗方法，对于具有不良预后特征的患者。纵隔原发部位和两种或更多种先前治疗线是最能预测不良 DFS 的因素。Beyer 和 Einhorn 模型可以帮助预测结果。
