Biological activity of celecoxib in the bronchial epithelium of current and former smokers.
Biological activity of celecoxib in the bronchial epithelium of current and former smokers.
复制标题
塞来昔布在当前和前吸烟者的支气管上皮中的生物学活性。
DOI：
10.1158/1940-6207.capr-09-0233
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发表时间：
2010-02
期刊：
影响因子：
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通讯作者：
Kurie JM
中科院分区：
文献类型：
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作者：
Kim ES;Hong WK;Lee JJ;Mao L;Morice RC;Liu DD;Jimenez CA;Eapen GA;Lotan R;Tang X;Newman RA;Wistuba II;Kurie JM
非小细胞肺癌（NSCLC）是西方国家癌症相关死亡的主要原因。解决这一问题的一个重要方法是制定有效的化学预防战略。在这项研究中，我们检测了环氧化酶-2 （COX-2）抑制剂塞来昔布是否在当前和以前吸烟者的支气管上皮中具有生物活性，正如细胞增殖降低所证明的那样。至少有20包年（包年=每天吸烟包数乘以吸烟年数）吸烟史的当前或既往吸烟者被随机分为四个治疗组（塞来昔布然后安慰剂，塞来昔布然后塞来昔布，安慰剂然后塞来昔布，或安慰剂然后安慰剂）之一，并在基线、3个月和6个月接受支气管镜检查和活检。204例患者主要为吸烟者（79.4%）；81人接受低剂量塞来昔布或安慰剂治疗，123人接受高剂量塞来昔布或安慰剂治疗。塞来昔布最初口服200毫克，每日两次，随后方案将剂量增加到400毫克，每日两次。主要终点是支气管上皮Ki-67标记的变化（从基线到3个月）。在参与者中未观察到心脏毒性。虽然低剂量治疗的效果不显著，但高剂量塞来昔布使前吸烟者的Ki-67标记降低了3.85%，使当前吸烟者的Ki-67标记降低了1.10%，在调整化生和吸烟状况后，显著高于安慰剂组（P = 0.02）。3 - 6个月的塞来昔布方案被证明是安全的。塞来昔布400mg bid在当前和以前吸烟者的支气管上皮中具有生物活性；关于塞来昔布在非小细胞肺癌化学预防中的疗效的进一步研究可能是有必要的。
Non-small-cell lung cancer (NSCLC) is the primary cause of cancer-related death in Western countries. One important approach taken to address this problem is the development of effective chemoprevention strategies. In this study, we examined whether the cyclooxygenase-2 (COX-2) inhibitor celecoxib, as evidenced by decreased cell proliferation, is biologically active in the bronchial epithelium of current and former smokers. Current or former smokers with at least a 20 pack-year (pack-year = number of packs of cigarettes per day times number of years smoked) smoking history were randomized into one of four treatment arms (3-month intervals of celecoxib then placebo, celecoxib then celecoxib, placebo then celecoxib, or placebo then placebo) and underwent bronchoscopies with biopsies at baseline, 3 months, and 6 months. The 204 patients were primarily (79.4%) current smokers; 81 received either low-dose celecoxib or placebo and 123 received either high-dose celecoxib or placebo. Celecoxib was originally administered orally at 200 mg twice daily and the protocol subsequently increased the dose to 400 mg twice daily. The primary endpoint was change in Ki-67 labeling (from baseline to 3 months) in bronchial epithelium. No cardiac toxicities were observed in the participants. Although the effect of low-dose treatment was not significant, high-dose celecoxib decreased Ki-67 labeling by 3.85% in former smokers and by 1.10% in current smokers—a significantly greater reduction (P = 0.02) than that seen with placebo after adjusting for metaplasia and smoking status. A 3–6-month celecoxib regimen proved safe to administer. Celecoxib 400 mg bid was biologically active in the bronchial epithelium of current and former smokers; additional studies on the efficacy of celecoxib in NSCLC chemoprevention may be warranted.