Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8852, USA.
Lung Cancer. 2012 Sep;77(3):567-71. doi: 10.1016/j.lungcan.2012.05.111. Epub 2012 Jul 4.
Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM.
Previously untreated MM patients with advanced, unresectable disease received cisplatin (75 mg/m(2)), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg) intravenously every 21 days for a maximum of 6 cycles. Patients with responsive or stable disease received bevacizumab (15 mg/kg) intravenously every 21 days until progression or intolerance. The primary endpoint was progression-free survival rate at 6 months.
53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6 months was 56% and the median progression-free survival was 6.9 months (95% confidence interval [CI], 5.3-7.8 months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8 months (95% CI; 10.0-17.0 months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients.
This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6 months compared with historical controls treated with cisplatin and pemetrexed alone.
恶性间皮瘤（MM）细胞表达血管内皮生长因子（VEGF）受体，并且在大多数人类间皮瘤活检标本中检测到 VEGF 蛋白表达。贝伐单抗是一种重组人源化单克隆抗体，可阻断 VEGF 与其受体的结合。我们评估了贝伐单抗联合顺铂和培美曲塞作为晚期不可切除 MM 患者的一线治疗。
先前未经治疗的晚期不可切除 MM 患者接受顺铂（75mg/m²）、培美曲塞（500mg/m²）和贝伐单抗（15mg/kg）静脉输注，每 21 天一次，最多 6 个周期。对有反应或稳定疾病的患者接受贝伐单抗（15mg/kg）静脉输注，每 21 天一次，直至进展或不耐受。主要终点是 6 个月时无进展生存率。
4 个中心共入组 53 例患者；其中 52 例可用于本分析。6 个月时无进展生存率为 56%，中位无进展生存期为 6.9 个月（95%置信区间[CI]，5.3-7.8 个月）。部分缓解率为 40%，35%的患者疾病稳定。中位总生存期为 14.8 个月（95%CI；10.0-17.0 个月）。3/4 级毒性包括中性粒细胞减少症（11%）、高血压（6%）和静脉血栓栓塞症（13%）。
这项评估贝伐单抗联合顺铂和培美曲塞在未经治疗的晚期 MM 患者中的试验未达到主要终点，即与单独接受顺铂和培美曲塞治疗的历史对照相比，6 个月时无进展生存率提高 33%。
