甲磺酸依喜替康（DX - 8951f）作为晚期非小细胞肺癌一线治疗的II期研究。

Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer.

作者信息

Braybrooke J P, Ranson M, Manegold C, Mattson K, Thatcher N, Cheverton P, Sekiguchi M, Suzuki M, Oyama R, Talbot D C

机构信息

Cancer Research UK Medical Oncology Unit, Churchill Hospital, Oxford OX3 7LJ, UK.

出版信息

Lung Cancer. 2003 Aug;41(2):215-9. doi: 10.1016/s0169-5002(03)00190-9.

DOI:10.1016/s0169-5002(03)00190-9

PMID:12871785

Abstract

BACKGROUND

Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m(2) per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one.

RESULTS

39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3-21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m(2), volume of distribution 18.2 l/m(2) and mean elimination half-life of 7.9 h.

CONCLUSIONS

Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.

摘要

背景

甲磺酸依喜替康（DX - 8951f）是一种喜树碱的水溶性类似物，可抑制拓扑异构酶I。这项多中心II期研究评估了单药依喜替康在先前未接受过治疗的晚期非小细胞肺癌（NSCLC）患者中的活性。

患者与方法

组织学或细胞学确诊为IIIb期或IV期NSCLC的患者接受依喜替康治疗，剂量为0.5mg/m²，每天静脉输注30分钟，共5天，每3周重复一次，最多进行6个周期。在研究入组前记录可测量的疾病情况，患者每两个周期重新分期。在第一个周期进行药代动力学（PK）采样。

结果

39例患者（32例ECOG体能状态为0或1；29例男性，10例女性；平均年龄63岁）进入研究。33例患者完成了至少两个周期的依喜替康治疗，11例完成了6个周期。2例患者（5.1%，95%置信区间0.3 - 21.3%）出现部分缓解，7例（18.0%）出现轻微缓解，8例（20.5%）病情稳定。肿瘤进展的中位时间（TTP）为88天，总生存中位时间为262天。主要毒性为可逆性中性粒细胞减少。依喜替康的PK分析显示平均清除率为2.28 l/h per m²，分布容积为18.2 l/m²，平均消除半衰期为7.9小时。