用无环维甲酸、聚戊烯酸预防肝细胞癌患者的第二原发性肿瘤。肝癌预防研究组。

Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group.

作者信息

Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki K T, Tanaka T, Tsurumi K, Okuno M, Tomita E, Nakamura T, Kojima T

机构信息

First Department of Internal Medicine, Gifu University School of Medicine, Japan.

出版信息

N Engl J Med. 1996 Jun 13;334(24):1561-7. doi: 10.1056/NEJM199606133342402.

DOI:10.1056/NEJM199606133342402

PMID:8628336

Abstract

BACKGROUND

In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment.

METHODS

We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma.

RESULTS

Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas--7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P = 0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31; 95 percent confidence interval, 0.12 to 0.78).

CONCLUSIONS

Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

摘要

背景

在肝细胞癌（肝癌）患者中，尽管进行了手术切除和经皮乙醇注射治疗，复发和第二原发性肝癌的发生率仍很高。我们研发了一种无环类视黄醇——聚戊烯酸，它在实验室中可抑制肝癌发生，并能诱导源自人肝癌的细胞系分化和凋亡。在一项随机对照研究中，我们测试了该化合物是否能降低根治性治疗后复发和第二原发性肝癌的发生率。

方法

我们前瞻性地研究了89例在原发性肝癌手术切除或经皮乙醇注射后无疾病的患者。我们将患者随机分为两组，一组接受聚戊烯酸（每日600毫克），另一组接受安慰剂，为期12个月。随机分组后，每三个月通过超声检查研究残余肝脏。该研究的主要终点是组织学确诊的复发性或新发肝癌的出现。

结果

聚戊烯酸治疗显著降低了复发性或新发肝癌的发生率。在中位随访38个月后，聚戊烯酸组有12例患者（27%）出现复发性或新发肝癌，而安慰剂组有22例患者（49%）出现，P = 0.04。最显著的差异在于第二原发性肝癌组——接受聚戊烯酸治疗的组中有7例，而安慰剂组中有20例（对数秩检验P = 0.04）。Cox比例风险分析表明，作为一个独立因素，聚戊烯酸降低了第二原发性肝癌的发生（调整后的相对风险为0.31；95%置信区间为0.12至0.78）。