在德国一项II期试验（AUO试验AB 35/09）中，使用紫杉醇和依维莫司对晚期尿路上皮癌进行二线治疗。

Second-Line Treatment of Advanced Urothelial Cancer with Paclitaxel and Everolimus in a German Phase II Trial (AUO Trial AB 35/09).

作者信息

Niegisch Günter, Retz Margitta, Thalgott Mark, Balabanov Stefan, Honecker Friedemann, Ohlmann Carsten Henning, Stöckle Michael, Bögemann Martin, Vom Dorp Frank, Gschwend Jürgen, Hartmann Arndt, Ohmann Christian, Albers Peter

机构信息

Department of Urology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

出版信息

Oncology. 2015;89(2):70-8. doi: 10.1159/000376551. Epub 2015 Mar 11.

DOI:10.1159/000376551

PMID:25765871

Abstract

OBJECTIVE

The efficacy of second-line treatment after failure of platinum-based chemotherapy in patients with advanced urothelial cancer is limited. Based on encouraging preclinical and clinical phase I data, we evaluated the safety and efficacy of the combination of paclitaxel and everolimus in these patients.

METHODS

In this trial, patients having failed to respond to prior platinum-based combination treatment of urothelial cancer were treated with paclitaxel (175 mg/m(2) i.v., 3-weekly) and the mTOR-inhibitor everolimus (10 mg p.o., once daily). The patients were treated until tumor progression or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the objective response rate (ORR) as the primary endpoint.

RESULTS

A total of 27 patients (67% male; median age 63 years) were enrolled. The most frequent grade III/IV toxicities were anemia (28%), peripheral neuropathy (28%), and fatigue (24%). No treatment-related deaths were reported. Complete and partial remissions were observed in 0/24 and 3/24 patients eligible for efficacy analysis, respectively (ORR 13%). Progression-free survival was 2.9 months [95% confidence interval (95% CI) 1.9-4.2], and the median overall survival was 5.6 months (95% CI 4.8-10.2).

CONCLUSION

The combination of paclitaxel and everolimus has not achieved the expected efficacy in second-line treatment of urothelial cancer and should not be further explored.

摘要

目的

晚期尿路上皮癌患者铂类化疗失败后的二线治疗疗效有限。基于令人鼓舞的临床前和临床I期数据，我们评估了紫杉醇与依维莫司联合用药在这些患者中的安全性和疗效。

方法

在本试验中，对先前铂类联合治疗尿路上皮癌无效的患者采用紫杉醇（175mg/m²静脉注射，每3周一次）和mTOR抑制剂依维莫司（10mg口服，每日一次）进行治疗。患者接受治疗直至肿瘤进展或最多完成6个周期。采用单阶段设计评估客观缓解率（ORR）作为主要终点。

结果

共纳入27例患者（67%为男性；中位年龄63岁）。最常见的III/IV级毒性反应为贫血（28%）、周围神经病变（28%）和疲劳（24%）。未报告与治疗相关的死亡病例。在符合疗效分析条件的24例患者中，分别有0例和3例观察到完全缓解和部分缓解（ORR为13%）。无进展生存期为2.9个月[95%置信区间（95%CI）1.9 - 4.2]，中位总生存期为5.6个月（95%CI 4.8 - 10.2）。