Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial
Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial
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DOI：
10.1007/s00280-005-0028-1
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发表时间：
2006-02-01
影响因子：
3
通讯作者：
Marini, G
中科院分区：
文献类型：
--
作者：
Ferrari, V;Valcamonico, F;Marini, G
引言：吉西他滨（GEM）单药治疗是胰腺癌的标准治疗。塞来昔布是一种选择性环氧合酶-2（考克斯-2）抑制剂。最近在人胰腺癌细胞系中的研究表明考克斯-2参与肿瘤依赖性血管生成，并为抑制考克斯通路作为有效的治疗方法提供了理论依据。本研究的目的是评价吉西他滨联合塞来昔布的毒性和活性。患者和方法：42例连续的经组织学或细胞学证实的胰腺癌患者进入试验。26例患者（pts）为转移性，16例患者为局部晚期疾病。方案包括GEM 1,000 mg/m2（30 min静脉输注），第1、8天，每3周一次，塞来昔布400 mg bid。结果：4名患者（9%）达到部分缓解，26名患者（62%）病情稳定，30名患者获得完全疾病控制（71% [95% CI，58-84%]）。23例患者（54.7% [95%CI，38.6-70.1%]）出现总体临床获益反应。未观察到4级中性粒细胞减少和3-4级血小板减少。在19%的患者中检测到3级中性粒细胞减少。3级非血液学毒性如下：肝毒性7%，恶心2.3%。3例患者（7%）和5例患者（12%）分别出现最小肌酐升高和水肿。中位生存期为9.1个月（95% CI，7.5-10.6个月）。结论：吉西他滨联合塞来昔布治疗急性毒性低，临床获益率高，疾病控制效果好。需要进一步的临床研究。
Introduction: Single agent gemcitabine (GEM) is the standard treatment of pancreatic adenocarcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Recent studies in human pancreatic tumor cell lines suggest an involvement of COX-2 in tumor-dependent angiogenesis and provide the rational for inhibition of the COX pathway as an effective therapeutic approach. The aim of this study is to evaluate the toxicity and activity of gemcitabine plus celecoxib. Patients and methods: Forty-two consecutive patients with histologically or cytologically confirmed pancreatic adenocarcinoma entered the trial. Twenty-six patients (pts) were metastatic, 16 pts had locally advanced disease. The schedule consisted of GEM 1,000 mg/m(2) (as a 30 min iv infusion) on days 1, 8 every 3 weeks and celecoxib 400 mg bid. Results: Four pts (9%) achieved a partial response and 26 (62%) had stable disease, gaining a total disease control in 30 pts (71% [95% CI, 58-84%]). Overall clinical benefit response was experienced by 23 pts (54.7% [95%CI, 38.6-70.1%]). Neither grade 4 neutropenia nor grade 3-4 thrombocytopenia was observed. Grade 3 neutropenia was detected in 19% of pts. Grade 3 non-hematological toxicity was as follows: hepatic toxicity 7%, nausea 2.3%. Three pts (7%) and 5 pts (12%) had respectively a minimum creatinine increase and edema. Median survival was 9.1 months (95% CI, 7.5-10.6 months). Conclusion: GEM in combination with celecoxib showed low toxicity, good clinical benefit rate and good disease control. Further clinical investigation is warranted.