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

Abstract

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).

Transcatheter arterial infusion chemotherapy with cisplatin in combination with transcatheter arterial chemoembolization decreases intrahepatic distant recurrence of unresectable hepatocellular carcinoma

“…Kamimura et al demonstrated a randomized trial for evaluating the effect of TAI using combination of miriplatin and cisplatin versus miriplatin alone. 37 They reported that the combination therapy of miriplatin and cisplatin had significantly better progression-free survival and overall DCR. Recently, as miriplatin has become the standard drug in addition to anthracyclines in TACE in Japan, [38][39][40] the results of the present study also provide useful basic information whether to add TAI using cisplatin to TACE using miriplatin in the future.…”

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

“…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.…”

“…We conducted a phase I study of the combination therapy and determined that both miriplatin and DDP-H can be administered up to the maximum tolerated dose of each drug without additional adverse effects[18]. Along with these results, we conducted a phase II study and confirmed the efficacy and safety of the combination therapy in cases with multiple HCC[19]. Here, we report two cases of patients with unresectable HCC who were successfully treated by miriplatin-TOCE/DDP-H-HAIC combination therapy, resulting in complete responses with no significant adverse events.…”