A Case of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Refractory to Epirubicin That Showed Marked Decrease in Tumor Markers after Transcatheter Arterial Infusion with Miriplatin

Nishikawa, Hiroki; Inuzuka, Tadashi; Takeda, Haruhiko; Nakajima, Jun; Sakamoto, Azusa; Henmi, Sinichiro; Ishikawa, T.; Saito, Sumio; Kita, Ryuichi; Kimura, Tōru; Osaki, Yukio; Koshikawa, Yorimitsu

doi:10.1159/000330106

Cited by 6 publications

(7 citation statements)

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“…It forms a stable suspension with lipiodol that gradually releases active derivatives in situ, which enables a higher localized concentration while circumventing spillover into systemic circulation [ 19 ]. Miriplatin has demonstrated antitumor effects and a promising safety profile [ 7 , 20 , 21 ]. In terms of chemotherapeutic agents for HAIC, platinum agents appear to be most effective.…”

Section: Discussionmentioning

confidence: 99%

“…These treatments take advantage of the fact that HCCs are fed to a greater extent by arterial blood than the surrounding liver parenchyma. Based on the fact that TOCE showed anti-tumor effects similar to TACE, especially in patients with multiple HCCs and a lower hepatic reserve [ 5 ], miriplatin, a third-generation platinum derivative with a lipophilic moiety that forms a suspension with lipiodol, was developed and approved for clinical use in Japan as a novel chemotherapeutic agent for use in TOCE [ 6 , 7 ]. On the other hand, HAIC can cover a larger area of the liver without reducing hepatic arterial flow, the combination of HAIC with TOCE [ 5 , 8 , 9 ] may improve treatment efficacy but retain an unfavorable toxicity profile.…”

Section: Introductionmentioning

confidence: 99%

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Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

et al. 2017

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BackgroundBased 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.MethodsNineteen 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.ResultsThe 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).ConclusionsThe 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.Trial registrationThis 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).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

et al. 2017

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“…In early non-responders, HAIC should not be continued; instead, different therapeutic options, including sorafenib, should be explored. We have experience of a case of advanced HCC with PVTT refractory to epirubicin that showed a marked decrease in tumor markers after HAIC with miriplatin [101]. …”

Section: Discussionmentioning

confidence: 99%

Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

Nishikawa

Osaki

Kita

et al. 2012

Cancers

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Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

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“…Additionally, miriplatin, a third-generation platinum agent that forms a stable suspension with lipiodol[7], was developed for TOCE in HCC and approved for clinical use in Japan as a novel chemotherapeutic agent[8-14]. On the other hand, HAIC can affect larger areas of the liver without reducing hepatic arterial flow[15].…”

Section: Introductionmentioning

confidence: 99%

“…Among these therapeutic options, TOCE showed equivalent therapeutic effect to TACE for many HCC patients with low hepatic reserve in a randomized phase III trial using zinostatin stimalamer dissolved in lipiodol[ 6 ]. Additionally, miriplatin, a third-generation platinum agent that forms a stable suspension with lipiodol[ 7 ], was developed for TOCE in HCC and approved for clinical use in Japan as a novel chemotherapeutic agent[ 8 - 14 ]. On the other hand, HAIC can affect larger areas of the liver without reducing hepatic arterial flow[ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Ogawa

Kamimura

Watanabe

et al. 2017

WJCC

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Hepatocellular carcinoma (HCC) is one of the most common cancers and the third highest cause of cancer-associated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization (TOCE), and hepatic arterial infusion chemotherapy (HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

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A Case of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Refractory to Epirubicin That Showed Marked Decrease in Tumor Markers after Transcatheter Arterial Infusion with Miriplatin

Cited by 6 publications

References 12 publications

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

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