Hepatocellular carcinoma (HCC) is the most common type of liver cancer
 and various therapeutic options have been developed by focusing on the specific tumour stage and hepatic functional reserve
[2–9]. A variety of transarterial treatments have been provided to cases at relatively advanced stages
, and these treatments were roughly divided into the following three groups: tran-sarterial chemoembolization (TACE), transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC), based on the likelihood of deteriorating hepatic reserve. TACE involves hepatic arterial injections of chemotherapeutic agents combined with embolizing materials. TOCE is solely an arterial administration of a combination of chemotherapeutic agents and oily contrast medium of lipiodol ultra fluid (Laboratory Guerbet, Aulnay-sous-Bois, France), while in TAC, chemotherapeutic agents alone are infused through the hepatic artery. Although TACE is only a transarterial procedure, for which therapeutic efficacy has been proved in randomised prospective controlled studies, the deterioration of hepatic reserve is estimated at 20%–58%, mainly because of ischaemic damage to the nontumourous background liver
[10, 11], inferring a higher risk of unfavourable reduction in hepatic reserve function in cases with poor hepatic reserve. Therefore, to develop a safe and efficient transarterial therapeutic procedure in such cases, other effective means of performing TOCE, TAC, and TOCE + TAC have been tested
TACE and TOCE were recently compared in a randomised phase III trial using zinostatin stimalamer dissolved in lipiodol
 with subsequent arterial embolization (TACE) or without embolization (TOCE). Interestingly, the results showed no improvement in survival rates by performing embolization and TOCE represented to be a therapeutic option for HCC patients with low hepatic reserve. However, two major concerns with TOCE are: 1) the method of combining water-based chemotherapeutic agents with oily lipiodol in a stable formulation; and 2) that TOCE is unable to target wide area of the liver as it reduces the hepatic arterial flow, although tentative, that may result in hepatic failure. For first concern, Miriplatin, a third-generation platinum derivative with lipophilic moiety that forms a suspension with lipiodol, was recently developed and approved for clinical use in Japan as a novel chemotherapeutic agent for HCC
[16–21] with promising results
[22–24]. For second concern, as TAC requires no embolization, that can be injected in wide area and its anti-tumour effect has been reported in several studies
[5, 13–15], followed by the promising results from a multicentre phase II study in patients with unresectable HCC using cisplatin (CDDP), a first-generation platinum agent, in which the response rate was recorded as 33.8%
, it might be effective to treat wide area of the liver with poor hepatic reserve function. In addition, the first-pass kinetics
 of CDDP by TAC contribute to the anti-tumor effect and decrease the adverse systemic events
. Since highly concentrated CDDP powder for TAC (DDP-H, IA-call®; Nippon Kayaku Co., Ltd) is available in Japan, TAC is now widely used in Japan to treat multiple small tumours or patients with poor hepatic reserve
[5, 13, 26].
Based on these results and the advances in the development of new chemotherapeutics, it is reasonable to consider the combination therapy of CDDP-TAC with miriplatin-TOCE to treat advanced stage HCC with poor hepatic reserve function safely and effectively. Therefore, in this study we conducted a phase I dose-escalation study on DDP-H-TAC followed by miriplatin-TOCE to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) in unresectable HCC. The safety issue with regard to the combination of two platinum-based chemotherapeutic agents will be discussed by referencing the pharmacokinetics of platinum.