Takami Yuko, Eguchi Susumu, Tateishi Masaki, Ryu Tomoki, Mikagi Kazuhiro, Wada Yoshiyuki, Saitsu Hideki
Department of Hepato-Biliary-Pancreatic Surgery and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1, Jigyohama, Chuo-ku, Fukuoka, 810-8563, Japan.
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Hepatol Int. 2016 Sep;10(5):799-806. doi: 10.1007/s12072-016-9704-y. Epub 2016 Feb 4.
Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment.
A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined.
The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1-year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1-year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211).
Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC.
由于肝细胞癌（HCC）的复发率很高，即使在进行了肝切除和微波消融等根治性治疗之后，仍需要能够有效抑制HCC复发的化学预防药物。最近发现环氧合酶-2（Cox-2）在HCC中过度表达。因此，Cox-2抑制剂可能为HCC提供一种化学预防疗法。这项随机对照试验（RCT）研究了临床使用的Cox-2抑制剂美洛昔康在初始根治性治疗后预防HCC复发的潜力。
2008年7月至2011年4月期间，共有232例连续患者在我院接受了肝切除和/或微波消融作为HCC的初始治疗。8例患者因肾功能差、非甾体抗炎药相关溃疡病史或多种癌症而被排除。其余224例患者被随机分为对照组（n = 113）或美洛昔康组（n = 111）。对于美洛昔康组的患者，尽可能长时间每天服用15 mg美洛昔康（5 mg，每日三次）。确定总生存期（OS）和无病生存期（DFS）率。
美洛昔康组的1年、3年和5年OS率分别为95.4%、82.4%和70.1%。对照组的相应OS率分别为98.2%、85.1%和71.5%（p = 0.9549）。美洛昔康组的相应DFS率分别为89.2%、53.9%和44.0%，对照组分别为86.5%、57.0%和43.4%（p = 0.6722）。在包括乙型或丙型肝炎病毒感染患者的亚组的OS和DFS中，美洛昔康组和对照组之间未发现显著差异。然而，在无病毒性肝炎患者（NBNC-HCC）的亚组分析中，美洛昔康组（1年DFS，92.3%；3年DFS，75.8%；5年DFS，70.4%）和对照组（1年DFS，83.3%；3年DFS，48.1%；5年DFS，未获得）之间的DFS存在显著差异（p = 0.0211）。
对于NBNC-HCC患者，给予Cox-2抑制剂美洛昔康可能有可能抑制初始根治性治疗后的HCC复发。
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