Cisplatin Powder Research Articles

No lipiodol, no beads-another transcatheter arterial chemoembolization (TACE) with fine cisplatin powder and porous gelatin particles for TACE-naïve, multifocal, up-to-seven out hepatocellular carcinoma.

The Japanese Interventional oncology group (JIVROSG) showed the efficacy and safety of nonselective transarterial chemoembolization (TACE) with fine cisplatin powder (diamminedichloroplatinum; DDP-H) (65 mg/m2) and porous gelatin particles (DDP-H TACE) without lipiodol for extensive multifocal hepatocellular carcinoma (HCC). However, there are no studies on this method following the JIVROSG study. Therefore, we aimed to evaluate the efficacy of this new DDP-H TACE and its effect on liver function. We retrospectively reviewed the medical records of TACE-naïve patients with multifocal HCC (Child-Pugh class A, up-to-seven out, no prior history of systemic therapy) who underwent whole-liver DDP-H TACE between January 2006 and December 2019. Sixty patients were included in this study. The median age of the patients was 71 (range, 35-88) years. The median maximum size of tumors was 26 (range, 8-184) mm; 86.7% of patients met the up-to-11 criteria out. The overall survival duration was 30.3 months. At the time of initial evaluation (median, 45 days), the overall response rate was 65.0%; the disease control rate was 86.7% based on the modified response evaluation criteria in solid tumors guideline. Although nine patients' liver function had deteriorated to Child-Pugh class B at initial evaluation, six of them recovered to Child-Pugh class A. Only three patients (5%) showed permanently impaired liver function. Whole-liver DDP-H TACE without lipiodol or beads effectively reduced tumors and preserved liver function.

Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma.

To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest. The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

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

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).

Early Decreases in α-Fetoprotein and Des-γ-carboxy Prothrombin Predict the Antitumor Effects of Hepatic Transarterial Infusion Chemotherapy with Cisplatin (CDDP) Powder in Patients with Advanced Hepatocellular Carcinoma.

Objective We retrospectively investigated the relationship between the tumor response and serial changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) during hepatic arterial infusion of a cisplatin powder formulation (CDDP powder) in patients with advanced hepatocellular carcinoma (HCC). Methods Seventy-six advanced HCC patients were analyzed. All HCC patients received high-concentration cisplatin (1.43 mg/mL) via the haptic artery at a dose of 65 mg/m(2). AFP and DCP were measured at baseline and four to eight weeks after treatment, and the antitumor responses were evaluated according to the response evaluation criteria in solid tumours (RECIST) criteria after one or two courses of treatment. The patients were classified into two groups, a decreased group and a non-decreased group, according to the change in the serum levels of AFP and DCP at four to eight weeks compared to baseline. Results The response to treatment of the decreased group (n=16) and non-decreased group (n=60) was complete response/partial response/stable disease/progressive disease (CR/PR/SD/PD) in 4/4/5/3 and 1/11/8/40 patients, respectively. The response rate and disease control rate of the decreased group were significantly higher than those of the non-decreased group (p=0.016 and p<0.001, respectively). The median survival time (MST) of the decreased/non-decreased groups were 25.9/10.6 months, respectively. The cumulative survival rates for the decreased group were significantly higher than those of the non-decreased group (p=0.042). In the multivariate analysis, vascular invasion and the decreased group were significant factors that affected the therapeutic efficacy. Conclusion A decrease in the levels of AFP and DCP after the first treatment with CDDP powder is a good predictor for the antitumor effect and the prognosis.

Efficient Loading of cisplatin into Superabsorbent Polymer Microsphere in the treatment of hepatocellular carcinoma.

Background: Although Superabsorbent Polymer (SAP) microsphere has been useful in treatment of multiple and large hepatocellular carcinoma, efficient loading procedure of cisplatin onto SAP was not established. Loading efficiency of cisplatin was evaluated from the viewpoint of passive concentration gradient and ionic strength. Methods: To load cisplatin into SAP particle, 50mg of cisplatin powder was dissolved in three manners of aqueous solutions: (a) 50mg of cisplatin powder plus 35ml of warmed physiological saline solution (0.9%), (b) 5ml of physiological saline solution (0.9%) plus a half of solution (5ml) of the product made from 50mg of cisplatin powder in 10ml of iohexol 350mgI/ml, and (c) 10ml of iohexol 350mgI/ml plus 0.25ml of 10% NaCl solution Results: Cisplatin dissolved sufficiently in all the three methods. Average amounts of loaded cisplatin into SAP particles were 1.7mg in solution (a), 6.6mg in solution (b), and 11.8mg in solution (c). Since alteration of ionic strength in the method (c) significantly affect the extent of SAP swelling, addition of 0.25ml of 10% NaCl was unquestionably necessary. Release of cisplatin from SAP was evidently gradual, showing 83.1% after 6 hours in static elution experiment and 68.6% after 1 hour in dynamic elution experiment. Conclusions: Cisplatin-loaded SAP may act as a drug delivery system for treatment of liver cancer, and loading of cisplatin should be consciously performed considering cisplatin concentration and ionic strength. (225words)

Radiofrequency ablation combined with chemolipiodolization in a porcine liver: Comparison of the pharmacokinetic analysis with cisplatin powder and miriplatin.

To compare the pharmacokinetics of radiofrequency (RF) ablation with chemolipiodolization using cisplatin (CDDP) powder and miriplatin (MPT) in a porcine liver. Twelve pigs were divided equally into four groups. After each CDDP powder-lipiodol suspension (n = 6; groups A and B) or MPT-lipiodol suspension (n = 6; groups C and D) was injected into the lateral left artery, one RF ablation was performed at the lateral left lobe of each pig. Six pigs (groups A and C) were killed on the same day as treatment, whereas the other pigs (groups B and D) were killed 7 days after the treatment. The platinum concentrations in venous blood were assayed at 15, 60 and 120 min, and 7 days after treatment. The platinum concentrations in the ablated area and the surrounding liver were also examined. Plasma platinum concentrations of the CDDP group peaked at 15 min, and then gradually diminished over time (μg units), while plasma platinum levels in the MPT group gradually increased over time (ng units). Liver tissue platinum concentrations of the CDDP group were significantly lower in non-ablative areas than in ablated areas at days 0 and 7, while liver concentrations of the MPT group were significantly higher in non-ablative areas than in ablated areas at day 7. MPT may be a suitable chemotherapeutic agent to stagnate platinum in the surrounding liver.

What Is the Most Effective Drug Delivery System for Cisplatin during the Treatment of Hepatic Tumors with Single-Session Transcatheter Chemotherapy? A Pilot Study

Background/AimsThe aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion therapy for hepatocellular carcinoma (HCC).MethodsWe divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gelatin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes.ResultsThe mean free cisplatin concentrations were as follows. For group A, the mean was 48.58 µg/mL at 0 minute, 7.31 µg/mL at 5 minutes, 5.70 µg/mL at 10 minutes, and 7.15 µg/mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 µg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 µg/mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C.ConclusionsThese results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver.

Cisplatin loaded PMMA: mechanical properties, surface analysis and effects on Saos-2 cell culture

Despite wide resection and systemic chemotherapy, bone tumors may present with local recurrences, metastases and pathological fractures. Application of bone cement containing antineoplastic drug to fill the defect after resection of metastatic lesions and to support implants has been suggested to prevent local tumor growth and implant failures. In this study, we aimed to demonstrate the effects of the addition of cisplatin which is a widely used antineoplastic drug for osteosarcoma, on the mechanical properties of bone cement, and to evaluate the cytotoxic effects of eluted cisplatin on Saos-2 cell culture. Two cement samples were prepared by mixing 100 mg and 300 mg of cisplatin powder with 40 g cement powder. The bone cement of the control group did not contain cisplatin. Mechanical analyses included 4-point bending, compression and shear testing. For cytotoxicity analysis, samples were incubated in Dulbecco's Modified Eagle's medium for 15 days. Mediums were applied to Saos-2 cell culture and cell viability was measured. Surface analyses were performed by scanning electron microscope (SEM). The addition of cisplatin did not alter the mechanical properties of bone cement. It was observed that the eluted cisplatin had cytotoxic effects on Saos-2 cells. SEM analyses demonstrated cisplatin granules on the surface of cement samples. Cisplatin maintains its cytotoxic property when released from bone cement without compromising the mechanical stability. Application of cisplatin loaded bone cement may help local control of tumor growth. We believe that our study will shed light on to these new practices for the treatment of bone cancers and will encourage future studies.

Transcatheter Arterial Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres for Colorectal Liver Metastases after FOLFOX Failure: Results of a Phase I/II Study

PurposeTo report the results of a phase I/II study of a transcatheter arterial chemoembolization protocol using cisplatin powder and degradable starch microspheres (DSM) for unresectable colorectal liver metastases after failure of FOLFOX (5-flourouracil, leucovorin plus oxaliplatin) chemotherapy conducted to determine the recommended dose of cisplatin powder and to assess the efficacy and safety of the protocol. Materials and MethodsA fine-powder formulation of cisplatin was mixed with DSM and administered via the hepatic artery every 4 weeks. In phase I, three cohorts of patients received escalating doses of cisplatin powder: 50 mg/m2, 65 mg/m2, and 80 mg/m2. In phase II, tumor response, toxicity, and survival times were assessed. ResultsThe study enrolled 24 patients. Previously, FOLFOX had been administered to all patients, an irinotecan-containing regimen had been administered to 12 patients, and bevacizumab or cetuximab or both had been administered to 14 patients. In phase I, dose-limiting toxicity did not appear at any level, and the recommended dose of cisplatin powder was determined to be 80 mg/m2. In phase II, a tumor response rate of 61.1% was achieved. The median hepatic progression-free survival and overall survival were 8.8 months (95% confidence interval [CI], 4.06–13.5 mo) and 21.1 months (95% CI, 8.37–33.8 mo). The following grade 3 toxicities were observed: thrombocytopenia (12.5%), aspartate transaminase elevation (33.3%), alanine transaminase elevation (12.5%), hyponatremia (8.3%), and cholecystitis (4.2%). ConclusionsThis study shows that transcatheter arterial chemoembolization with cisplatin powder at a dose of 80 mg/m2 mixed with DSM is well tolerated and can produce a high response rate with a long survival time for patients with unresectable colorectal liver metastases after failure of FOLFOX.

Phase I/II Multicenter Study of Transarterial Chemoembolization with a Cisplatin Fine Powder and Porous Gelatin Particles for Unresectable Hepatocellular Carcinoma: Japan Interventional Radiology in Oncology Study Group Study 0401

PurposeA multicenter phase I/II study of transarterial chemoembolization with a fine cisplatin powder and gelatin particles (GPs) for multifocal hepatocellular carcinoma (HCC) was conducted. Primary endpoints were dose-limiting toxicity (DLT) and recommended dose (RD). Secondary endpoints were the incidence and severity of adverse events and tumor response. Materials and MethodsNonselective transarterial chemoembolization was performed until all tumor enhancement disappeared. Lipiodol was not used. In the phase I study, the cisplatin dose was escalated from 35 mg/m2 to 65 mg/m2 in 15-mg/m2 increments to determine DLT and RD. In the phase II study, 40 patients were treated with the RD. Toxicity was assessed by Common Toxicity Criteria for Adverse Effects (version 3.0), and tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) and European Association for the Study of the Liver (EASL) criteria. ResultsA total of 46 patients were enrolled. As no DLT occurred at any dose level in the phase I study, RD was determined as 65 mg/m2. In the phase II study, the treatment was discontinued in one patient as a result of vasovagal response. Toxicities of grade 3 or higher included nausea (2.2%), pancreatitis (2.2%), cholecystitis (2.2%), thrombocytopenia (8.7%), hyperbilirubinemia (2.2%), and increased aspartate aminotransferase (28.3%) and alanine aminotransferase (21.7%) levels. Tumor response rates under RD were 25.6% and 64.1% by RECIST and EASL criteria, respectively. ConclusionsNonselective transarterial chemoembolization with fine cisplatin powder and GPs was well tolerated and effective in patients with multifocal HCC at the RD of 65 mg/m2.

Abstract No. 35: Comparative study of short-term therapeutic effects of miriplatin-lipiodol suspension and cisplatin-lipiodol suspension in transcatheter arterial chemo-embolization for hepatocellular carcinoma

Miriplatin hydrate (Miripla; Dainippon Sumitomo Pharma Co. Ltd. Osaka, Japan) was released in 2010 and has been developed in Japan. Miriplatin contains a lipophilic platinum complex with a higher affinity for iodized oil than the cisplatin powder. The purpose of this study was to investigate the short-term therapeutic effects and adverse effects associated with the use of Miriplatin-lipiodol suspension in TACE for HCC as a single-institution retrospective study, using a cisplatin-lipiodol suspension as a control.

Phase I/II study of transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres for unresectable hepatic metastases from colorectal cancer refractory to systemic standard chemotherapy.

577 Background: We conducted a phase I/II study of novel transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres (DSM) to determine the recommended dose (RD) and to assess the efficacy and safety. Methods: Cisplatin powder and DSM mixing solution was administered followed by the injection of DSM alone via hepatic artery every 4 weeks. In phase I, cohorts of 3 patients received escalating dose of cisplatin (50, 65 and 80mg/m2), and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response, toxicity, hepatic progression free survival (H-PFS) and 6-month overall survival (OS) rate. Results: A total of 24 patients (male 16, female 8; mean age 63.0, range 45-79; colon 15, rectal 9) were enrolled in this study. FOLFOX had previously been administered to all patients, irinotecan-containing regimen to 12 and bevacizumab and/or cetuximab to 14. During phase I (n= 9 patients), maximum tolerated dose was not reached and cisplatin 80 mg/m2 was recommended for a phase II. Phase II enrolled 15 patients. The following grade 3 toxicities were observed: platelets reduction 16.6%, aspartate transaminase elevation 38.8%, alanine transaminase elevation 16.6%, hyponatremia 11.1%, cholecystitis 5.5%. The tumor response rate was 53.3% (CR 0, PR 8, SD 6, and PD 1). The median H-PFS was 6.3 months (95% CI; 2.71 to 9.88) and 6 -month OS rate was 86.7%. Conclusions: This phase I/II study demonstrates that novel transcatheter arterial chemoembolization with 80 mg/m2 cisplatin powder and DSM is well tolerable, and can produce a high response rate with encouraging survival duration. Further clinical trials are warranted. No significant financial relationships to disclose.

Phase II study of segmental transcatheter arterial chemoembolization using ethiodized oil mixed with cisplatin powder for unresectable hepatocellular carcinoma.

292 Background: Conventional transcatheter arterial chemoembolization (TACE) using with ethiodized oil mixed with epirubicin or doxorubicin hydrochloride mainly has been widely adapted for intermediate-stage hepatocellular carcinoma (HCC). However, cisplatin has stronger effect for HCC than epirubicin and in the recent years cisplatin powder was commercially available in Japan and then we can use cisplatin powder mixed with ethiodized oil for HCC. We conducted a phase II study to assess the safety and efficacy of segmental or subsegmental (Seg/Subseg) TACE using a suspension of cisplatin powder mixed with ethiodized oil for unresectable HCC. Methods: Twenty patients with single-nodule HCC that was not indicated for surgical treatment or local ablation therapy were enrolled in this study. Seg/Subseg-TACE was performed by using a 2-F tip microcatheter at a distal portion of the subsegmental artery supplying the tumor. Subsequently, the feeding artery was embolized with gelatin sponge particles. The suspension was prepared by mixing 100 mg of cisplatin powder with 10 ml of ethiodized oil. Primary endpoint of this phase II trial was 2-year local disease free survival (DFS); secondary endpoints evaluated were the safety, time to progression (TTP), and 2-year overall survival (OS) rate. Results: A total of 20 patients (male 15, female 5; mean age 72.4, range 62-83; Child Pugh's A 20) were treated single nodule HCC with Seg/subseg TACE. Median tumor size was 2.6cm (range1.2-5.0cm). The 2-year local DFS was 63.2 %. The following grade 3 or 4 toxicities were observed: platelets reduction 5%, aspartate transaminase elevation 55%, alanine transaminase elevation 40% and alkaline phosphatase elevation 5%. The median TTP was 17.6 months (95%CI, 5.25 to 29.9) and the 2-year OS rate was 94.7%. Conclusions: This phase II study demonstrates that segmental or subsegmental transcatheter arterial chemoembolization using a suspension of cisplatin powder mixed with ethiodized oil is well tolerable, and may achieve significant local tumor control and prolong survival. Further clinical trials are warranted. No significant financial relationships to disclose.

Hepatic Arterial Infusion Therapy with a Fine Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

We retrospectively evaluated the antitumor effect, survival and toxicities of hepatic arterial infusion therapy using a fine powder formulation of cisplatin (cisplatin powder) in hepatocellular carcinoma patients with portal vein tumor thrombosis. Twenty-four patients classified as Child-Pugh class A or B underwent a single session of hepatic arterial infusion therapy using cisplatin powder. The treatment was repeated every 4-6 weeks in patients with no evidence of tumor progression or unacceptable toxicity. The treatment response was evaluated using contrast-enhanced computed tomography performed 1 month after each treatment. The survival rate was evaluated using the Kaplan-Meier method, and predictors of a better outcome were identified using univariate analysis. The mean follow-up period was 11.2 months (range, 1.3-44.2 months). A total of 57 sessions of intra-arterial infusion (1-6 sessions per patient; mean, 2.4 sessions) with cisplatin powder were performed. A complete response and a partial response were obtained in one and four patients, respectively (objective response rate = 20.8%). The median survival time for all the patients was 7.0 months; the median survival times for the 5 responders and 19 non-responders were 37.3 and 5.6 months, respectively. The 1- and 2-year survival rates were 38% and 16%, respectively. Significant prognostic factors related to survival were the therapeutic effect, patient age and serum alanine aminotransferase level. Severe adverse reactions resulting in treatment discontinuation were not observed, and all the toxicities were successfully managed using conservative treatment. Hepatic arterial infusion therapy with a fine powder formulation of cisplatin was safe, well-tolerated and might help to prolong the life span of advanced hepatocellular carcinoma patients with portal vein tumor thrombosis.

In Vitro Characterization of Cisplatin-loaded Superabsorbent Polymer Microspheres Designed for Chemoembolization

To find appropriate contrast media to load cisplatin into superabsorbent polymer (SAP) and to analyze the absorption and elution kinetics of cisplatin to and from SAP. Three contrast media-ioxaglic acid 320 mg/mL, iohexol 300 mg/mL, and iopamidol 300 mg/mL-were tested for solubility of a new highly soluble cisplatin powder. The appropriate concentrations of cisplatin were predetermined according to the solubility in each contrast medium. For each concentration, we assessed the cisplatin elution kinetics with an atomic absorption spectrophotometer. The SAP particle diameters (106-150 microm dry size) before and after drug elution were also measured. The concentrations of cisplatin were predetermined as 2.5 mg/mL in ioxaglic acid, 2.5 mg/mL in iohexol, and 5.0 mg/mL in iohexol. At these concentrations, 100 mg of SAP carried 5 mg, 25 mg, and 50 mg of cisplatin dissolved in ioxaglic acid (2.5 mg/mL) and iohexol (2.5 mg/mL and 5.0 mg/mL), respectively. Cisplatin-loaded SAP in ioxaglic acid and iohexol exhibited similar elution profiles, with cisplatin fractions of 15%, 40%, 70%, and 95% at 1, 3, 6, and 24 hours, respectively. By drug elution, the mean particle diameter changed from 0.31 mm to 0.61 mm in ioxaglic acid (2.5 mg/mL), from 0.54 mm to 0.60 mm in iohexol 2.5 mg/mL, and from 0.63 mm to 0.59 mm in iohexol 5.0 mg/mL. SAP was confirmed to absorb and elute cisplatin within 24 hours. When mixed with iohexol, SAP carried a ten times larger dose of cisplatin and expanded twice as large as when mixed with ioxaglic acid. Cisplatin-loaded SAP may have potential as a drug delivery system for the clinical treatment of liver tumors.

Abstract No. 171: Phase I Study of Transcatheter Arterial Chemoembolization with Cisplatin Powder and Degradable Starch Microspheres for Unresectable Hepatic Metastases from Colorectal Cancer

Abstract No. 171: Phase I Study of Transcatheter Arterial Chemoembolization with Cisplatin Powder and Degradable Starch Microspheres for Unresectable Hepatic Metastases from Colorectal Cancer

Transarterial Chemoembolization Using Cisplatin Powder in a Rabbit Model of Liver Cancer

The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 microg/ml for the cisplatin-HAI group, 1.23 microg/ml for the cisplatin-GS-TACE group, and 12.65 microg/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 microg/ml for the cisplatin-HAI group, 1.13 microg/ml for the cisplatin-GS-TACE group, and 1.09 microg/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

Successful Management of Multiple Liver Metastases From Pancreatic Neuroendocrine Tumor by Hepatic Arterial Administration of Cisplatin Powder

Successful Management of Multiple Liver Metastases From Pancreatic Neuroendocrine Tumor by Hepatic Arterial Administration of Cisplatin Powder

A Novel, Evolutionarily Conserved Protein Phosphatase Complex Involved in Cisplatin Sensitivity

Using a combination of tandem affinity purification tagging and mass spectrometry, we characterized a novel, evolutionarily conserved protein phosphatase 4 (PP4)-containing complex (PP4cs, protein phosphatase 4, cisplatin-sensitive complex) that plays a critical role in the eukaryotic DNA damage response. PP4cs is comprised of the catalytic subunit PP4C; a known regulatory subunit, PP4R2; and a novel protein that we termed PP4R3. The Saccharomyces cerevisiae PP4R3 ortholog Psy2 was identified previously in a screen for sensitivity to the DNA-damaging agent and anticancer drug cisplatin. We demonstrated that deletion of any of the PP4cs complex orthologs in S. cerevisiae elicited cisplatin hypersensitivity. Furthermore human PP4R3 complemented the yeast psy2 deletion, and Drosophila melanogaster lacking functional PP4R3 (flfl) exhibited cisplatin hypersensitivity, suggesting a highly conserved role for PP4cs in DNA damage repair. Finally we found that PP4R3 may target PP4cs to the DNA damage repair machinery at least in part via an interaction with Rad53 (CHK2).

A randomized clinical trial of cisplatin solution and cisplatin powder combination regimens in the treatment of patients with lung cancer

To compare the efficacy and side effects between cisplatin solution and cisplatin powder combination regimens for lung cancer. A total of 223 patients were enrolled into this study. EP protocol was given to patients with small cell lung cancer (SCLC), and NP protocol to non small cell lung cancer (NSCLC). The 223 patients were randomly divided into cisplatin solution group and cisplatin powder group, and the same drugs and dosage were used in the two groups for the same type of lung cancer. Response rates of the cisplatin solution group and the cisplatin powder group were 84.8% and 82.4% for SCLC ( P > 0.05), and 31.6% and 29.9% for NSCLC ( P > 0.05), respectively. The major side effects were gastrointestinal reactions and myelosuppression. Significantly higher incidence of nausea/vomiting was found in cisplatin solution group than that in cisplatin powder group for either SCLC or NSCLC ( P < 0.05). There was a remarkable difference in cost of hospitalization between the two groups ( P < 0.05). Cisplatin solution is as effective as cisplatin powder in the treatment of lung cancer. However, the more severe nausea/vomiting reactions and higher cost of cisplatin solution should be considered in its clinical application.