Randomized, double-blind, placebo-controlled phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia
Randomized, double-blind, placebo-controlled phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia
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DOI：
10.1158/1078-0432.ccr-1020-3
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发表时间：
2004-03-01
影响因子：
11.5
通讯作者：
Cavanaugh, PF
中科院分区：
文献类型：
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作者：
Mulshine, JL;Atkinson, JC;Cavanaugh, PF
目的：非选择性环氧合酶（考克斯）抑制剂已被报道可降低上呼吸消化道癌症的发生率。酮咯酸氨丁三醇口腔冲洗液已被证明可以解决另一个COX依赖性过程，牙周病，而不会引起胃肠道副作用。该试验评估了含有酮咯酸的局部递送口腔冲洗液在减少口腔白斑面积方面是否与单独的口腔冲洗液一样安全且更有效。实验设计：57名患者随机（比例2：1）参加一项双盲、安慰剂对照研究，研究对象为酮咯酸（10 ml 0.1%酮咯酸冲洗液; n = 38）或安慰剂（10 ml冲洗液; n = 19），每天给药两次，持续30秒，持续90天。主要终点通过视觉评估，在入组时和90天时获得白斑病变大小的二维测量值。次要终点是组织学评估的白斑作为采样的串行打孔活检和独立审查由三个pathologist.Results：患者包括67%的男性，11%非高加索人，86%使用烟草，两组之间没有显着差异。两种冲洗剂耐受性良好，依从性良好，不良事件无显著差异（P = 0.27）。主要反应率（完全反应和部分反应）为30%酮咯酸和32%的安慰剂arm. There是没有显着差异，在组织学变化之间的两个arms.Conclusion：局部交付的含COX口腔冲洗耐受性良好，但没有产生显着减少白斑的程度与安慰剂相比。然而，安慰剂组的良好应答率仍无法解释，需要对酮咯酸的组织渗透进行额外研究。
Purpose: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia.Experimental Design: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists.Results: The patients included 67% males, 11% nonCaucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms.Conclusion: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.