Diamond Jennifer R, Wu Benjamin, Agarwal Neeraj, Bowles Daniel W, Lam Elaine T, Werner Theresa L, Rasmussen Erik, Gamelin Erick, Soto Felipe, Friberg Greg, Sun Yu-Nien, Sharma Sunil
Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, 80045, USA,
Invest New Drugs. 2015 Jun;33(3):691-9. doi: 10.1007/s10637-015-0236-4. Epub 2015 Apr 21.
Trebananib is an anti-angiogenic peptibody under investigation in patients with advanced cancer. This study evaluated the pharmacokinetic (PK) drug-drug interaction of paclitaxel and trebananib.
Patients with advanced solid tumors received weekly 80 mg/m(2) intravenous (IV) paclitaxel (3 weeks on/1 week off) with weekly 15 mg/kg IV trebananib starting at Week 2. Blood samples for PK analysis were collected at Week 1 (paclitaxel alone), Week 6 (paclitaxel and trebananib), and Week 8 (trebananib alone). An absence of interaction was to be concluded if the 90 % confidence intervals (CI) for the differences in paclitaxel exposure fell within the 0.80-1.25 interval.
The primary study was conducted between 7/2012 and 10/2013. Thirty-five patients were enrolled and 34 received both treatments. Most patients were white (91 %) and female (59 %); mean age was 61 years. The most common tumor types were ovarian (32 %) and bladder (27 %), 71 % of patients had stage IV disease, and all had Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. PK parameter analysis was done on patients with evaluable PK data at both assessments (with and without concomitant therapy; n = 28). The geometric least squares mean (GLSM) ratio (90 % CI) of paclitaxel AUCinf with and without trebananib was 1.17 (1.10, 1.25). The GLSM ratio (90 % CI) of trebananib AUCtau,ss with and without paclitaxel was 0.92 (0.87, 0.97). The most common adverse events were fatigue, local edema, peripheral edema, and nausea.
This study showed no evidence of clinically meaningful PK interaction between paclitaxel and trebananib.
曲贝替定是一种正在晚期癌症患者中进行研究的抗血管生成肽抗体。本研究评估了紫杉醇与曲贝替定的药代动力学（PK）药物相互作用。
晚期实体瘤患者从第2周开始每周接受80mg/m²静脉注射（IV）紫杉醇（3周用药/1周停药），同时每周接受15mg/kg静脉注射曲贝替定。在第1周（仅使用紫杉醇）、第6周（使用紫杉醇和曲贝替定）和第8周（仅使用曲贝替定）采集用于PK分析的血样。如果紫杉醇暴露差异的90%置信区间（CI）落在0.80 - 1.25区间内，则得出不存在相互作用的结论。
主要研究于2012年7月至2013年10月进行。35名患者入组，34名接受了两种治疗。大多数患者为白人（91%）和女性（59%）；平均年龄为61岁。最常见的肿瘤类型是卵巢癌（32%）和膀胱癌（27%），71%的患者为IV期疾病，所有患者东部肿瘤协作组（ECOG）评分为0或1。对两次评估（有和无联合治疗）时具有可评估PK数据的患者（n = 28）进行PK参数分析。有和无曲贝替定情况下紫杉醇AUCinf的几何最小二乘均值（GLSM）比值（90%CI）为1.17（1.10，1.25）。有和无紫杉醇情况下曲贝替定AUCtau,ss的GLSM比值（90%CI）为0.92（0.87，0.97）。最常见的不良事件为疲劳、局部水肿、外周水肿和恶心。
本研究未显示紫杉醇与曲贝替定之间存在具有临床意义的PK相互作用的证据。
