A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.
A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.
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DOI：
10.1186/1471-2407-6-285
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发表时间：
2006-12-11
期刊：
影响因子：
3.8
通讯作者：
Nippgen J
中科院分区：
文献类型：
--
作者：
Friess H;Langrehr JM;Oettle H;Raedle J;Niedergethmann M;Dittrich C;Hossfeld DK;Stöger H;Neyns B;Herzog P;Piedbois P;Dobrowolski F;Scheithauer W;Hawkins R;Katz F;Balcke P;Vermorken J;van Belle S;Davidson N;Esteve AA;Castellano D;Kleeff J;Tempia-Caliera AA;Kovar A;Nippgen J
抗血管生成治疗被认为至少在高度血管化的肿瘤如胰腺癌中具有膀胱抑制作用。在这项研究中，血管生成抑制剂西仑吉肽和吉西他滨的治疗效果与吉西他滨单独治疗晚期不可切除的胰腺癌患者进行了比较。在7个国家的20个中心进行了一项多国、开放标签、对照、随机、平行组、II期初步研究。西仑吉肽以600 mg/m2每周两次给药，每个周期给药4周，吉西他滨以1000 mg/m2给药3周，然后每个周期停药1周。计划的治疗期为6个4周周期。研究的主要终点是总生存期，次要终点是无进展生存期（PFS）、缓解率、生活质量（QoL）、对疾病生物标志物（CA 19.9）和血管生成（血管内皮生长因子和碱性成纤维细胞生长因子）的影响以及安全性。一项辅助研究调查了两种药物在一个患者亚组中的药代动力学。89例患者接受了随机化。西仑吉肽和吉西他滨组的中位总生存期为6.7个月，吉西他滨单药组为7.7个月。中位PFS时间分别为3.6个月和3.8个月。总有效率分别为17%和14%，肿瘤生长控制率分别为54%和56%。CA 19.9水平的变化与疾病的临床过程一致，但与血管生成的生物标志物没有明显的关系。治疗组间的QoL和安全性评价相当。药代动力学研究显示吉西他滨对西仑吉肽的药代动力学参数无影响，反之亦然。两组之间在疗效、安全性和QoL方面未观察到具有临床意义的差异。观察结果在该背景下的其他临床研究范围内。联合方案耐受性良好，对任一药物的安全性、耐受性和药代动力学均无不良影响。
Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer. A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients. Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa. There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.
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影响因子：
6.2
作者：
Colucci, G;Giuliani, F;Lopez, M
通讯作者：
Lopez, M
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
8.4
作者：
Brooks, PC
通讯作者：
Brooks, PC
影响因子：
8.4
作者：
Eskens, FALM;Dumez, H;van Oosterom, AT
通讯作者：
van Oosterom, AT
影响因子：
4
作者：
Haller, DG
通讯作者：
Haller, DG