Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
J Thorac Oncol. 2010 Mar;5(3):354-60. doi: 10.1097/JTO.0b013e3181c7307e.
Bevacizumab (B) improves survival of patients with metastatic, nonsquamous non-small cell lung cancer. Based on encouraging results from preclinical studies combining B with sunitinib (S), a phase II, randomized, open-label study (Study Assessing the Blockade of both VEGF Receptor and ligand to enhance Efficacy in Lung) was initiated to assess clinical outcomes of adding S to paclitaxel (P)/carboplatin (C) + B (PCB) for first-line treatment of locally advanced, metastatic, or recurrent nonsquamous non-small cell lung cancer.
Study enrollment was to occur in three phases. In the first phase, patients received PC + B (15 mg/kg every 3 weeks), +/-S (25 mg daily, 2 weeks on, 1 week off). If tolerated, the second phase would include a third cohort receiving 37.5 mg S. The third phase would consist of PCB +/- highest tolerable dose S.
Between March 2007 and January 2008, 26 patients were randomized to receive PCB and 30 to PCB + S 25 mg. Because of poor tolerability, none of the patients were escalated to 37.5 mg S. Median treatment duration was 10.3 weeks for PCB and 6.0 weeks for PCB + S. Thirty-five percent of patients on PCB + S required S dose reduction, 52% required S treatment interruption, and 59% discontinued S because of adverse events, most frequently hematologic events (neutropenia, thrombocytopenia, and leukopenia) and fatigue. Patients receiving PCB + S required more B interruptions (38% versus 19% for PCB) and discontinuation (52% versus 35%) because of adverse events. Survival data were limited by small sample sizes and limited treatment duration. Overall survival was not mature at time of analysis: median 6.6 months for PCB + S and not reached for PCB. Two out of 25 efficacy-evaluable patients randomized to the PCB + S cohort had confirmed partial responses, compared with 5 of 19 randomized to the PCB cohort.
The addition of S to PCB was not well tolerated because of toxicities. This combination should not be studied further at these doses and schedules.
贝伐单抗（B）可提高转移性非鳞状非小细胞肺癌患者的生存率。基于临床前研究中联合使用 B 和舒尼替尼（S）的令人鼓舞的结果，开展了一项 II 期、随机、开放标签的研究（评估阻断血管内皮生长因子受体和配体以提高肺疗效的研究），以评估在紫杉醇（P）/卡铂（C）+B（PCB）一线治疗局部晚期、转移性或复发性非鳞状非小细胞肺癌中添加 S 的临床结果。
研究入组分三个阶段进行。第一阶段，患者接受 PC+B（每 3 周 15 mg/kg），+/-S（每日 25 mg，2 周给药，1 周停药）。如果耐受良好，第二阶段将包括接受 37.5 mg S 的第三个队列。第三阶段将包括 PCB+/-最高耐受剂量 S。
2007 年 3 月至 2008 年 1 月期间，26 例患者被随机分配接受 PCB 治疗，30 例患者接受 PCB+S 25 mg 治疗。由于耐受性差，没有患者升级至 37.5 mg S。PCB 的中位治疗持续时间为 10.3 周，PCB+S 为 6.0 周。35%的 PCB+S 组患者需要减少 S 剂量，52%需要中断 S 治疗，59%因不良事件（主要为血液学事件[中性粒细胞减少症、血小板减少症和白细胞减少症]和疲劳）而停止 S 治疗。接受 PCB+S 的患者因不良事件需要更多的 B 中断（38%对 PCB 的 19%）和停药（52%对 PCB 的 35%）。由于样本量小和治疗持续时间有限，生存数据有限。分析时总体生存尚未成熟：PCB+S 的中位生存期为 6.6 个月，而 PCB 组尚未达到。在接受 PCB+S 治疗的 25 例可评估疗效的患者中，有 2 例确认部分缓解，而在接受 PCB 治疗的 19 例患者中，有 5 例确认部分缓解。
由于毒性作用，PCB 中添加 S 不能耐受。在这些剂量和方案下，不应进一步研究这种组合。
