MAXIMUM TOLERATED SYSTEMIC EXPOSURE (MTSE) TO TOPOTECAN

本研究将评估在卡铂和依托泊苷的标准一线方案中添加拓扑替康治疗广泛期SCLC的效果。基于拓扑替康在SCLC中的活性及其新的作用机制，在卡铂和依托泊苷的基础上添加拓扑替康可能提高广泛期SCLC患者的缓解率和中位生存期。本研究的目的如下：1)评估拓泊替康与卡铂、依托泊苷联合应用于广泛期SCLC患者全身靶向暴露的可行性。2)确定拓扑替康联合卡铂和依托泊苷在广泛分期SCLC患者中的最大耐受全身暴露量（MTSE）。3)评估广泛分期SCLC患者接受卡铂、拓扑替康和依托泊苷治疗的有效率、疾病进展时间和总生存期。4)在该患者群体中，内酯和拓扑替康总清除率与肾小球滤过率相关。

This study will assess the addition of topotecan to the standard, first-line regimen of carboplatin and etoposide for the treatment of extensive stage SCLC. Based on its activity in SCLC and its novel mechanism of action, the addition of topotecan to carboplatin and etoposide may improve the response rate and median survival in extensive stage SCLD patients. The study objectives are as follows: 1) To evaluate the feasibility of targeting systemic exposure of topotecan when used in combination with carboplatin and etoposide in patients with extensive stage SCLC. 2) To define the maximum tolerated systemic exposure (MTSE) of topotecan in combination with carboplatin and etopside in extensive stage SCLC patients. 3) To assess the response rate, the time to disease progression, and overall survival of patients receiving carboplatin, topotecan and etoposide in extensive stage SCLC patients. 4) To correlate lactone and total topotecan clearance with glomerular filtration rate in this patient population.