Kamimura Kenya, Suda Takeshi, Yokoo Takeshi, Kamimura Hiroteru, Kanefuji Tsutomu, Tsuchiya Atsunori, Takamura Masaaki, Kawai Hirokazu, Waguri Nobuo, Yamagiwa Satoshi, Terai Shuji
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan.
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, 949-7302, Niigata, Japan.
BMC Cancer. 2017 May 10;17(1):322. doi: 10.1186/s12885-017-3320-7.
Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.
Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.
The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).
The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.
This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).
基于一项关于使用米铂和顺铂粉末联合进行肝动脉灌注化疗（DDP-H）治疗不可切除肝细胞癌的I期研究（UMIN-CTR000003541）取得的有前景的结果，开展了一项多中心、开放标签、随机II期研究，以评估联合治疗与米铂单药治疗的疗效和安全性。
19例患者，分别为5例巴塞罗那临床肝癌分期分类A期和14例B期病例，被随机分配接受米铂单药治疗（n = 9）或米铂/DDP-H联合治疗（n = 10）。DDP-H和/或米铂通过供应含有肿瘤的肝叶的肝动脉给药，除其他次要终点外，无进展生存期被分析作为主要终点。除非记录到疾病进展或严重不良事件，否则重复相应治疗。
单药治疗或联合治疗分别共进行了15次或36次疗程。虽然两组在治疗间隔（p = 0.96）或每次疗程使用的米铂剂量（p = 0.99）方面无显著差异，但联合治疗组的无进展生存期和总体疾病控制率显著更好（分别为91天对423天，p = 0.025；40.0%对77.8%，p = 0.0025）。与这些观察结果一致，观察到去γ-羧基凝血酶原的增加趋势明显较慢，联合治疗组的治疗疗程数几乎显著更多（分别为p < 0.0001，p = 0.057）。相反，中位生存时间未显示显著差异（单药治疗706天对联合治疗733天；p = 0.40）。仅在接受联合治疗的患者治疗过程中观察到胆碱酯酶显著下降（r = -0.86，p < 0.0001）。两组均有少数病例出现血液学和/或非血液学毒性，被分类为1级（美国国立癌症研究所常见不良反应事件评价标准）。
米铂与DDP-H联合使用具有更高的疾病控制效果，表明它是多灶性肝癌病例的一种有前景的替代治疗方法，特别是对于那些能够耐受治疗而肝储备无降低的患者。
本研究于2012年1月1日在大学医院医学信息网络临床试验注册中心注册（http://www.umin.ac.jp/ctr/index.htm，UMIN000004691）。
