Lammers Philip Edward, Lu Bo, Horn Leora, Shyr Yu, Keedy Vicki
Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee, USA;
Thomas Jefferson University, Philadelphia, Pennsylvania;
Oncologist. 2015 May;20(5):491-2. doi: 10.1634/theoncologist.2015-0030. Epub 2015 Apr 6.
The concomitant use of weekly nab-paclitaxel and carboplatin with concurrent radiotherapy was demonstrated to be a safe therapeutic approach in this phase I trial of 10 evaluable patients with stage III NSCLC.Despite the lack of systemic glucocorticoids, there were no reported infusion reactions or cases of peripheral neuropathy in this trial, both of which are known to occur with the use of paclitaxel.
Unresectable stage III non-small cell lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent chemoradiotherapy results in significant toxicity with the use of current chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug Administration in October 2012 for use along with carboplatin in advanced NSCLC. This study was undertaken to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with carboplatin and concurrent radiotherapy in patients with unresectable stage III NSCLC.
Escalating doses of once-weekly nab-paclitaxel were given along with once-weekly carboplatin area under the plasma concentration time curve (AUC) of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of carboplatin and nab-paclitaxel consolidation chemotherapy.
Eleven patients were enrolled and received treatment per protocol, with 10 evaluable for efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m(2)), 2 DLTs were observed: esophagitis and radiation dermatitis. Six patients were enrolled at dose level 0 (nab-paclitaxel 40 mg/m(2)) with no DLTs. Nine of 10 evaluable patients had a partial response.
Concurrent chemoradiotherapy with nab-paclitaxel 40 mg/m(2) and carboplatin AUC 2 is a safe and well-tolerated therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study to evaluate the efficacy of this regimen is under way.
在这项针对10例可评估的III期非小细胞肺癌患者的I期试验中，每周使用白蛋白结合型紫杉醇和卡铂并同步放疗被证明是一种安全的治疗方法。尽管未使用全身性糖皮质激素，但该试验中未报告有输注反应或周围神经病变病例，而这两种情况在使用紫杉醇时均已知会发生。
不可切除的III期非小细胞肺癌（NSCLC）的5年生存率为20%，并且使用当前的化疗药物进行同步放化疗会导致显著的毒性。白蛋白结合型紫杉醇于2012年10月被美国食品药品监督管理局批准与卡铂联合用于晚期NSCLC。本研究旨在确定不可切除的III期NSCLC患者每周使用白蛋白结合型紫杉醇联合卡铂及同步放疗的最大耐受剂量和剂量限制毒性（DLTs）。
每周递增剂量给予白蛋白结合型紫杉醇，同时每周给予血浆浓度-时间曲线下面积（AUC）为2的卡铂，并同步进行66 Gy分33次的放疗，随后进行2个周期的卡铂和白蛋白结合型紫杉醇巩固化疗。
11例患者入组并按方案接受治疗，其中10例可评估疗效和毒性。在剂量水平1（白蛋白结合型紫杉醇60 mg/m²）时，观察到2例DLTs：食管炎和放射性皮炎。6例患者入组剂量水平0（白蛋白结合型紫杉醇40 mg/m²），未出现DLTs。10例可评估患者中有9例出现部分缓解。
对于III期NSCLC患者，白蛋白结合型紫杉醇40 mg/m²联合卡铂AUC 2的同步放化疗是一种安全且耐受性良好的治疗方案。一项评估该方案疗效的单独的I/II期研究正在进行中。
