A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours.
A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours.
复制标题
一项针对多发性生殖细胞肿瘤患者使用基于拓扑异构酶 I 的方法进行的 II 期研究。
作者：
J. Shamash;T. Powles;K. Mutsvangwa;P. Wilson;W. Ansell;E. Walsh;Daniel M. Berney;J. Stebbing;T. Oliver
背景
生殖细胞肿瘤(GCTS)患者复发不止一次或复发为纵隔原发肿瘤，其预后很差。我们已经证明，拓扑异构酶1可能是复发GCT的一个有吸引力的靶点。我们研究了伊立替康、紫杉醇和奥沙利铂(IPO)以及基于拓扑替康的大剂量治疗在有反应的患者中的作用。
患者和方法
28名多次复发的性腺和纵隔GCT患者参加了这项第二阶段的研究。所有患者都接受了IPO化疗，12例(43%)继续接受大剂量治疗。采用Kaplan-Meier方法对这些患者的预后进行评估，中位无进展的随访时间为1年。
结果
治疗有效20例(71%)，其中完全缓解5例(18%)，部分缓解13例(46%)，部分缓解2例(7%)。9名患者(32%)继续无进展，目前整个组的中位生存期为17个月。在随后接受大剂量巩固治疗的12名患者中，有7名(58%)保持无进展。最常见的III/IV级毒性是感染(68%)，没有IPO相关的中毒死亡；有1人死于大剂量治疗。
结论
以拓扑异构酶I为基础、缺乏依托泊苷的IPO化疗对复发性GCT非常有效。这一数据值得进一步调查。
BACKGROUND
The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population.
PATIENTS AND METHODS
Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow-up of 1 year.
RESULTS
Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy.
CONCLUSION
Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation.