A Phase II Study of Celecoxib in Combination with Paclitaxel, Carboplatin, and Radiotherapy for Patients with Inoperable Stage IIIA/B Non-Small Cell Lung Cancer
A Phase II Study of Celecoxib in Combination with Paclitaxel, Carboplatin, and Radiotherapy for Patients with Inoperable Stage IIIA/B Non-Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-08-0629
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发表时间：
2009-03-15
影响因子：
11.5
通讯作者：
Choy, Hak
中科院分区：
文献类型：
--
作者：
Mutter, Robert;Lu, Bo;Choy, Hak
目的：环氧化酶（考克斯）-2表达上调在肺癌的发生发展中起重要作用。选择性考克斯-2抑制剂促进了化疗敏感性和放射敏感性的肿瘤细胞在临床前试验。实验设计：在一个单一的机构第二阶段的研究，我们试图确定的有效性，同时给予塞来昔布和生物标志物检测预测响应考克斯-2 inhibition.Results：17例IIIA或IIIB期非小细胞肺癌（NSCLC）被纳入研究。在试验期间，所有患者均接受400 mg塞来昔布每日两次连续治疗，同时接受紫杉醇和卡铂的同步放化疗。塞来昔布治疗持续至疾病进展。总客观缓解率为42.9%，中位总生存期为203天。与无应答者相比，塞来昔布给药1周后，完全和部分应答患者的尿11 α-羟基-9，15-二氧代-2，3，4，5-四去甲前列烷-1，20-二酸（前列腺素E-2的主要代谢产物PGE-M）水平显著降低。在开始治疗前PGE-M水平非常高的患者对治疗的反应也很差。血清血管内皮生长因子水平没有预测响应或survival.Conclusion：试验被终止，因为它没有达到预定的目标，80%的总有效率。对于不能手术的IIIA/B期NSCLC患者，在同步放化疗的基础上加用塞来昔B不能改善生存率。尿PGE-M是预测NSCLC患者对考克斯-2抑制的反应的一种有前景的生物标志物。
Purpose: Cyclooxygenase (COX)-2 up-regulation plays an important role in the pathogenesis of lung cancer. Selective COX-2 inhibitors have promoted chemosensitivity and radiosensitivity of tumor cells in preclinical trials.Experimental Design: In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition.Results: Seventeen patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled in the study. All received 400 mg celecoxib twice daily continuously while on trial in addition to concurrent chemoradiation therapy with paclitaxel and carboplatin. Celecoxib was continued until disease progression. The overall objective response rate was 42.9%, and the median overall survival time was 203 days. In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11 alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E-2, after 1 week of celecoxib administration. Patients with very high levels of PGE-M before initiation of therapy also responded poorly to therapy. Serum vascular endothelial growth factor levels did not predict response or survival.Conclusion: The trial was terminated because it did not meet the predetermined goal of 80% overall response rate. In unselected patients, the addition of celecoxib to concurrent chemoradiotherapy with inoperable stage IIIA/B NSCLC does not improve survival. Urinary PGE-M is a promising biomarker for predicting response to COX-2 inhibition in NSCLC.