Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma.
Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma.
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DOI：
10.1186/1471-230x-12-127
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发表时间：
2012-09-20
影响因子：
2.4
通讯作者：
Aoyagi Y
中科院分区：
文献类型：
--
作者：
Kamimura K;Suda T;Tamura Y;Takamura M;Yokoo T;Igarashi M;Kawai H;Yamagiwa S;Nomoto M;Aoyagi Y
对于肝脏储备功能较差的肝细胞癌（HCC）患者，目前尚无标准治疗程序。随着新开发的化疗药物米铂的获批，我们首先开展了CDDP粉剂（DDP-H）与米铂联合治疗的I期研究，报告了其治疗此类不可切除的HCC的安全性和有效性。确定使用米瑞铂和 DDP-H 联合经动脉油性化疗栓塞 (TOCE) 和经动脉化疗 (TAC) 治疗不可切除的肝细胞癌 (HCC) 的最大耐受剂量 (MTD) 和剂量限制毒性 (DLT)。使用DDP-H的经动脉化疗是通过增加DDP-H的剂量（35-65mg/m2）通过肝固有动脉靶向HCC结节，然后通过米铂经动脉油性化疗栓塞靶向HCC结节。本研究共有 9 名患者入组，在所有接受 80mg（中位数，18-120）米铂的病例中，任何剂量的 DDP-H 均未观察到 DLT。 1 名患者获得部分缓解的抗肿瘤疗效评级，而总共 4 名患者（8 名接受评估的患者）表现出稳定的疾病缓解，疾病控制率达到 62.5%。药代动力学结果显示，服用米铂后血浆铂浓度没有进一步增加。我们的结果表明，DDP-H 和米铂的组合可以在各自的 MTD 内安全地用于治疗 HCC。这项研究已在大学医院医学信息网络临床试验注册中心注册（UMIN-CTR000003541）。
There is no standard therapeutic procedure for the hepatocellular carcinoma (HCC) in patients with poor hepatic reserve function. With the approval of newly developed chemotherapeutic agent of miriplatin, we have firstly conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination therapy and reported its safety and efficacy for treating unresectable HCC in such cases. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating unresectable hepatocellular carcinoma (HCC). Transarterial chemotherapy using DDP-H was performed through the proper hepatic artery targeting the HCC nodules by increasing the dose of DDP-H (35–65 mg/m2) followed by targeting the HCC nodules by transarterial oily chemoembolization with miriplatin. A total of nine patients were enrolled in this study and no DLT was observed with any dose of DDP-H in all cases in whom 80 mg (median, 18–120) miriplatin was administered. An anti-tumour efficacy rating for partial response was obtained in one patient, while a total of four patients (among eight evaluated) showed stable disease response, leading to 62.5% of disease control rate. The pharmacokinetic results showed no further increase in plasma platinum concentration following miriplatin administration. Our results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).