Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)

Watanabe, Shobu; Nitta, Norihisa; Ohta, Shin‐ichi; Sonoda, Akinaga; Otani, Hideji; Tomozawa, Yuki; Nitta-Seko, Ayumi; Tsuchiya, Keiko; Tanka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi

doi:10.1007/s00270-011-0172-4

Cited by 13 publications

(12 citation statements)

References 29 publications

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“…In a multicenter phase II study that enrolled unresectable HCC cases [10], the response rate for cisplatin was 33.8%, whereas the response rates were 15%–20% for epirubicin [9] and mitomycin C [8]. Because miriplatin shows no cross-resistance with different generations of platinum agents [6, 22, 23], we examined double platinum treatments and anticipated additive effects of miriplatin and DDP-H, which currently provides the highest concentration of CDDP. The phase I study of this combination therapy showed no dose-limiting toxicity at a maximum dose of 120 mg/body for TOCE [24] and 65 mg/m 2 for HAIC.…”

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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“…Although various chemotherapeutic agents have been used for treating HCC[16,17], platinum agents achieved a better response rate in a multicenter phase II study enrolling patients with unresectable HCC[29]. Based on these results and the fact that miriplatin showed no cross-resistance with different generations of platinum agents[30], we conducted a phase I study[18] and a phase II study[19] of combined therapy with miriplatin-TOCE and DDP-H-HAIC and demonstrated its safety and efficacy for patients with unresectable HCC. In fact, we could repeat the miriplatin-TOCE/DDP-H-HAIC combination therapy for the two cases in the present study without severe adverse effects.…”

Section: Discussionmentioning

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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“…Treatment in few HCC cases has shown cross-resistance with different generations of platinum agents [16,21,29]. In a rat model, miriplatin exhibited higher anti-tumour activity and lower hepatic toxicity than CDDP-lipiodol [16], and promising results have been reported in HCC patients [22-24].…”

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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Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)

Abstract: We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.

Cited by 13 publications

References 29 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

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

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

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