A Phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer
A Phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer
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DOI：
10.1007/s10637-005-1028-z
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Philip, PA
中科院分区：
文献类型：
--
作者：
El-Rayes, BF;Zalupski, MM;Philip, PA
背景。胰腺癌是最具化疗耐药性的恶性肿瘤之一。环氧合酶-2 （COX-2）酶的表达在肿瘤进展和治疗抵抗中起重要作用。一项11期研究旨在确定吉西他滨固定剂量输注（FDR）、顺铂和COX-2抑制剂塞来昔布（celecoxib）对转移性胰腺癌患者6个月生存率的影响。入选标准包括病理或细胞学确诊的胰腺腺癌。先前不允许使用吉西他滨治疗。患者接受吉西他滨1000mg /m(2)超过100分钟的联合治疗，顺铂35mg /m(2)在第1天和第8天静脉注射，塞来昔布连续每日剂量为800mg。每21 d重复一个周期。22例转移性胰腺癌患者入组（中位年龄59.5岁；男：女，13:9）。中位周期数为每位患者2个。中位生存时间为5.8个月（90% CI, 3.6-7.6个月）。6个月生存率为46% （90% CI, 27-62%）。主要毒性为中性粒细胞减少，65%的患者出现3级或4级毒性。在晚期胰腺癌患者中，塞来昔布加入吉西他滨（通过FDR）和顺铂并没有增加化疗双联体的活性。单独使用塞来昔布可能不足以使胰腺癌对常规细胞毒性治疗的效果敏感。
Background. Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase 11 study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer.Methods. The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1000 mg/m(2) over 100 minutes, cisplatin 35 mg/m(2) I.V. on days 1 and 8, and celecoxib continuously at a daily dose of 800 mg. Cycles were repeated every 21 days.Results. Twenty-two patients with metastatic pancreas cancer were enrolled (median age, 59.5 years; M:F, 13:9). The median number of cycles was 2 per patient. The median survival time was 5.8 months (90% CI, 3.6-7.6 months). The probability of survival at 6 months was 46% (90% CI, 27-62%). The major toxicity was neutropenia with grade 3 or 4 toxicities seen in 65% of patients.Conclusions. The addition of celecoxib to gemcitabine (by FDR) and cisplatin did not appear to increase activity of the chemotherapy doublet in patients with advanced pancreatic cancer. Celecoxib alone may not be sufficient to sensitize pancreatic cancer to the effects of conventional cytotoxic therapy.