Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab - an eastern cooperative oncology group study
Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab - an eastern cooperative oncology group study
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DOI：
10.1158/1078-0432.ccr-07-1154
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发表时间：
2008-03-01
影响因子：
11.5
通讯作者：
Johnson, David H.
中科院分区：
文献类型：
--
作者：
Dowlati, Afshin;Gray, Robert;Johnson, David H.
背景：E4599是一项II/III期试验，将878名晚期非小细胞肺癌患者随机分为卡铂+紫杉醇(PC ARM)或PC+贝伐单抗(BPC ARM)。存活率和无进展存活率均优于BPC组。相关研究中使用的标记物的基础是血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(BFGF)、可溶性细胞间黏附分子(ICAM)和E-选择素在多种恶性肿瘤中的升高以及对内皮细胞凋亡的反应。材料和方法：前瞻性相关检测包括治疗前、治疗前和治疗7周时血浆中血管内皮生长因子、碱性成纤维细胞生长因子、ICAM和E-选择素的变化。结果：E-选择素(P<；0.0001)在第7周较基线水平下降，碱性成纤维细胞生长因子(P=0.004)升高，两组差异无统计学意义(P>0.05)。基线ICAM显示两组患者的反应和存活率显著相关。无论采用何种治疗手段，低基线ICAM患者的有效率(32%比14%；P=0.02)、总生存率(P=0.00005)和1年生存率(65%比25%)均高于高ICAM患者。与PC相比，VEGF水平高的患者对BPC的反应更大，但这并不能预测患者的存活率。结果还表明，贝伐单抗对基线ICAM水平较低的患者有好处(无进展生存风险降低53%)。结论：在这项研究中，基线ICAM水平可以预测患者的预后，并预测使用或不使用贝伐单抗的化疗反应。血管内皮生长因子水平可预测贝伐单抗的疗效，但不能预测存活率。
Background: E4599 was a phase II/phase III trial, in which 878 patients with advanced non-small cell lung cancer were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (BPC arm). Survival and progression-free survival were superior on the BPC arm. The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble intercellular adhesion molecule (ICAM) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis.Materials and Methods: Prospective correlates included measurements of pretreatment plasma VEGF, as well as pretreatment and week 7, bFGF, ICAM, and E-selectin. Low and high levels were defined as less than or equal to or more than the median.Results: E-selectin (P < 0.0001) showed a decrease and bFGF showed an increase (P = 0.004) from baseline at week 7, which were similar in both arms. Baseline ICAM showed significant associations with response and survival in both groups. Patients with low baseline ICAM had a higher response rate (32% versus 14%; P = 0.02), better overall survival (P = 0.00005), and better 1-year survival (65% versus 25%) than those with high ICAM, respectively, regardless of treatment arm. Patients with high VEGF levels were more likely to respond to BPC compared with PC, but this was not predictive of survival. The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels (53% reduction in the progression-free survival hazard rate).Conclusions: In this study, baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab. VEGF levels were predictive of response to bevacizumab but not survival.