Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.
BMC Gastroenterol. 2012 Sep 20;12:127. doi: 10.1186/1471-230X-12-127.
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/m(2)) 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).
对于肝功能储备不良的肝细胞癌（HCC）患者，尚无标准的治疗程序。随着新型化疗药物米立膦酸的批准，我们首次进行了 CDDP 粉末（DDP-H）和米立膦酸联合治疗的 I 期研究，并报告了其治疗此类不可切除 HCC 的安全性和有效性。为了确定经动脉油化学栓塞（TOCE）和经动脉化疗（TAC）联合使用米立膦酸和 DDP-H 治疗不可切除肝细胞癌（HCC）的最大耐受剂量（MTD）和剂量限制毒性（DLT）。
通过增加 DDP-H（35-65mg/m2）的剂量，通过肝固有动脉靶向 HCC 结节，进行经动脉化疗，然后用米立膦酸靶向 HCC 结节进行经动脉油化学栓塞。
本研究共纳入 9 例患者，所有患者 DDP-H 剂量均未观察到 DLT，其中 80mg（中位数，18-120）米立膦酸给药。1 例患者获得部分缓解的抗肿瘤疗效评价，共有 4 例（8 例评价中）患者显示疾病稳定，疾病控制率为 62.5%。药代动力学结果显示，米立膦酸给药后血浆铂浓度无进一步升高。
我们的结果表明，DDP-H 和米立膦酸联合治疗 HCC 可安全地达到各自的 MTD。
本研究在大学医院医疗信息网络临床试验注册中心（UMIN-CTR000003541）注册。
