Future perspectives on the treatment of hepatocellular carcinoma with cisplatin

Ishikawa, Toru

doi:10.4254/wjh.v1.i1.8

Cited by 35 publications

(46 citation statements)

References 45 publications

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“…Because the therapeutic strategy is determined by both hepatic functional reserve and tumor stage, only 30% of HCC cases can benefit from therapies of locoregional control, such as surgical resection, radio frequency ablation, and heavy particle radiotherapy [8, 15, 16]. TACE or sorafenib are options when the tumor stage advances beyond locoregional control.…”

Section: Discussionmentioning

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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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%

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 contrast, TOCE and TAC can be provided over a broad range of cases as these are performed without arterial embolization and their efficacy has been reported [5,13-15,26]. Among various chemotherapeutic agents such as epirubicin [15] and mitomycin C [5], which carry a 15%–20% response rate, platinum agents appear to be the most promising as CDDP-TAC achieved a response rate of 33.8% in a multicentre phase II study enrolling unresectable HCC cases [13]. To investigate the highly effective and less toxic combination of TOCE and TAC, this study focused on safety issues associated with the concomitant use of two platinum agents.…”

Section: Discussionmentioning

confidence: 99%

Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma

et al. 2012

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BackgroundThere 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).MethodsTransarterial 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.ResultsA 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.ConclusionOur results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC.Trial registrationThis study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).

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“…Conventionally, anthracycline chemotherapeutic agents have been used in the HAI regimen; although, recently, platinum compounds have been used to treat HCC. 9 Cisplatin is a chemotherapeutic agent that consists of a platinum complex compound. It is linked to DNA chains in cells through passive diffusion and active transport; then, it exerts an apoptotic effect by inhibiting DNA synthesis and subsequent cell division.…”

Section: Discussionmentioning

confidence: 99%

Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma

Ishikawa

Higuchi

Kubota

et al. 2011

Cancer

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BACKGROUND:The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinumbased chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR). METHODS: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR. RESULTS: Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model. CONCLUSIONS: HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC.

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Future perspectives on the treatment of hepatocellular carcinoma with cisplatin

Cited by 35 publications

References 45 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

Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma

Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma

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