德国睾丸癌研究组进行的序贯剂量强化异环磷酰胺、顺铂、依托泊苷联合紫杉醇作为预后不良生殖细胞肿瘤诱导化疗的Ⅰ/Ⅱ期研究。

Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German Testicular Cancer Study Group.

作者信息

Hartmann Jörg T, Gauler Thomas, Metzner Bernd, Gerl Arthur, Casper Jochen, Rick Oliver, Horger Marius, Schleicher Jan, Derigs Günter, Mayer-Steinacker Regine, Beyer Jörg, Kuczyk Markus A, Bokemeyer Carsten

机构信息

Department of Oncology, South West German Comprehensive Cancer Center, Eberhard-Karls-University of Tuebingen, Otfried-Mueller-Str 10, 72076 Tuebingen, Germany.

出版信息

J Clin Oncol. 2007 Dec 20;25(36):5742-7. doi: 10.1200/JCO.2007.11.9099.

DOI:10.1200/JCO.2007.11.9099

PMID:18089869

Abstract

PURPOSE

To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features.

PATIENTS AND METHODS

Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2, ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC.

RESULTS

Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/microL and thrombocytes less than 25,000/microL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively.

CONCLUSION

Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.

摘要

目的

评估序贯、剂量强化化疗联合紫杉醇及外周血来源造血干细胞支持（PBSC）用于国际生殖细胞共识癌症组预后特征较差的初治转移性生殖细胞肿瘤（GCT）患者的可行性及毒性。

患者与方法

在高剂量（HD）依托泊苷、异环磷酰胺和顺铂（VIP；依托泊苷1500mg/m²、异环磷酰胺10000mg/m²和顺铂100mg/m²；累积剂量；每周期第-6至-2天）基础上，于第-6天添加三个剂量水平（135、175和225mg/m²）的紫杉醇。周期由PBSC和粒细胞集落刺激因子支持。在开始HD-VIP加紫杉醇周期之前，先给予一个周期的标准VIP以采集自体PBSC。

结果

53例接受152个周期治疗的患者中有52例可评估。正如预期，骨髓抑制是主要不良反应。白细胞低于1000/μL和血小板低于25000/μL的中位持续时间分别为6天和4天，与应用的紫杉醇剂量无关。5%的患者出现WHO 2级神经毒性和3级脑病。观察到的其他主要不良反应为口腔炎、腹泻和便秘。79%的患者对化疗加二次手术获得良好反应。存活患者中位随访时间41个月后，计算得出的2年和5年生存率分别为77.6%（95%CI，65.4%至89.9%）和75.2%（95%CI，62.5%至87.8%）。