A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable?
A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable?
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DOI：
10.1007/s10637-008-9127-2
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发表时间：
2008-10-01
影响因子：
3.4
通讯作者：
Tempero, Margaret A.
中科院分区：
文献类型：
--
作者：
Ko, Andrew H.;Dito, Elizabeth;Tempero, Margaret A.
背景：贝伐单抗是一种针对血管内皮生长因子的重组人源化单克隆抗体，其在胰腺癌治疗中的作用尚不清楚。本研究的目的是确定转移性胰腺癌化疗初治患者接受贝伐单抗联合固定剂量吉西他滨（FDR）和低剂量顺铂的安全性和有效性。方法：符合条件的患者在28天周期的第1天和第15天接受吉西他滨1000mg /m2 FDR输注（10mg /m(2) /分钟），顺铂20mg /m(2)，贝伐单抗10mg /kg。通过每两个周期的计算机断层扫描和每月的血清CA19-9测量来监测患者。结果：在符合分析条件的52例患者中，10例（19.2%）有未证实的反应，30例（57.7%）病情稳定。在35例基线CA19-9水平升高的患者中，20例（57.1%）在治疗期间出现>= 50%的生物标志物下降。到肿瘤进展的中位时间为6.6个月，中位生存期为8.2个月（估计1年生存率为36%）。可能与贝伐单抗相关的3/4级毒性包括血栓栓塞事件（15.1%）、高血压（13.2%）、胃肠道出血（9.4%）、心脏事件（7.5%）和肠穿孔（5.7%）。血浆血管内皮生长因子和碱性成纤维细胞生长因子水平和循环肿瘤细胞浓度与总生存率无关，无论是基线还是治疗2个月后。结论：这种含贝伐单抗的研究方案对转移性胰腺癌患者适度有效，尽管偶尔可能发生严重并发症。考虑到CALGB 80303的阴性结果，未来的努力应该集中在确定那些最有可能从贝伐单抗治疗中获益的特定患者上。
Background: The role of bevacizumab, a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor, in the treatment of pancreatic cancer remains unclear. The objectives of this study were to determine safety and efficacy in chemotherapy-naive patients with metastatic pancreatic cancer receiving bevacizumab in combination with fixed-dose rate (FDR) gemcitabine and low-dose cisplatin. Methods: Eligible patients received gemcitabine 1,000 mg/m2 at FDR infusion (10 mg/m(2) per minute), cisplatin 20 mg/m(2), and bevacizumab 10 mg/kg, on days 1 and 15 of a 28-day cycle. Patients were monitored by computed tomography scans every two cycles and monthly serum CA19-9 measurements. Results: Of 52 patients eligible for analysis, ten (19.2%) had an unconfirmed response and 30 (57.7%) had stable disease. Of 35 patients with elevated baseline CA19-9 levels, 20 (57.1%) had >= 50% biomarker decline during treatment. Median time to tumor progression was 6.6 months and median survival was 8.2 months (estimated 1-year survival, 36%). Grade 3/4 toxicities possibly related to bevacizumab included thromboembolic events (15.1%), hypertension (13.2%), gastrointestinal bleeding (9.4%), cardiac events (7.5%), and bowel perforation (5.7%). Plasma vascular endothelial growth factor and basic fibroblast growth factor levels and circulating tumor cell concentration did not correlate with overall survival, either at baseline or after 2 months of therapy. Conclusions: This bevacizumab-containing study regimen is modestly effective in patients with metastatic pancreatic cancer, although occasional serious complications may occur. Given the negative results of CALGB 80303, future efforts should be focused on identifying those specific patients who are most likely to benefit from bevacizumab-based therapy.