Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma

Favoulet, P; Cercueil, Jean-Pierre; Fauré, Philippe; Osmak, Liliana; Isambert, Nicolás; Beltramo, Jean Luc; Cognet, F.; Krausé, D.; Bedenne, Laurent; Chauffert, Bruno

doi:10.1097/00001813-200111000-00003

Cited by 32 publications

(24 citation statements)

References 20 publications

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“…On the contrary, the phase separation for lipiodolidarubicin emulsion was very limited (5 % aqueous solution and 95 % persisting emulsion); fluorescent electronic microscopy revealed that idarubicin was inside and at the periphery of lipid droplets as a result of drug-lipid ionic interactions. This enhanced emulsion stability is probably an advantage in increasing the contact time of the drug with cancer cells, as previously reported [30].…”

Section: Discussionsupporting

confidence: 75%

“…We took advantage of the higher lipophilicity of idarubicin, resulting in a great accumulation of the drug in the oily phase, thereby permitting lipiodol to act as a slow-releasing vector. Favoulet et al [30] demonstrated that lipiodol-doxorubicin emulsion was completely separated into two phases (oil and aqueous) after only 20 min. This might explain the pharmacokinetic data demonstrating that the intra-arterial administration of doxorubicin emulsified with lipiodol has little effect compared with intravenous administration of doxorubicin alone [31].…”

Section: Discussionmentioning

confidence: 99%

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Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Favelier

Boulin

Hamza

et al. 2012

Cardiovasc Intervent Radiol

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Background There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin. Methods In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated. Results Postembolization syndrome was observed after 30.9 % (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3-5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19 % (4 of 21) of patients. On imaging, no progression was encountered; four patients (24 %) exhibited stable disease, 12 (57 %) exhibited a partial response, and five (19 %) exhibited a complete response. Median TTTF was 16.7 months (Kaplan-Meier analysis). At 6 months, 94.7 % (95 % confidence interval [CI] 68.1-99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6 % (95 % CI 21.6-73.9) of patients at 1 year. Overall survival was 83.5 % (95 % CI 57-94.4) at 1 year. Conclusion Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Favelier

Boulin

Hamza

et al. 2012

Cardiovasc Intervent Radiol

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“…5,6 Anticancer drug delivery by hepatic arterial chemoembolization using GSP and/or IOE has been widely used in clinical settings to treat HCC efficiently, without significantly changing hepatic function due to the liver's duplex blood supply systems. 7,8 Although it is not via blood vessel, an efficient and localized transgene expression has been successfully achieved using gelatin sponge sheets (GSS) in a rat Achilles tendon (for 17 days) and mouse cochlea. 11,12 Taken these findings together, we hypothesized that catheter-mediated hepatic arterial embolization with GSP would enhance transgene expression efficiency into hepatocytes, because of the low clearance rate and long contact time of adenovirus soaked in GSP.…”

Section: Resultsmentioning

confidence: 99%

“…5,6 Transcatheter hepatic arterial chemoembolization using emulsions of anticancer agents, iodized oil esters (IOE) and/or GSP has been determined to be an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC), offering prolonged survival and good life quality. 7,8 As GSP induces embolization and is absorbed slowly, without inducing excessive inflammatory reaction or irritation, 8 anticancer agents soaked in GSP are released slowly into the liver environment. We asked whether adenoviral vectors, rather than anticancer drugs soaked in emulsion of GSP, might be released slowly after catheter-mediated embolization, a process that we hoped might increase transduction efficiency and/ or decrease viral clearance.…”

mentioning

confidence: 99%

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes

et al. 2004

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Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant b-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.

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“…After embolization of APS, the routine interventional therapy was done for the tumor, as reported [11][12][13][14][15] . After catheter was inserted into feeding artery of tumour, pirarubicin (THP)/lipiodol(LPD) emulsion was injected through catheter for the patients without tumour thrombus in main portal vein.…”

Section: Treatmentsmentioning

confidence: 99%

Comparison of long-term effects between intra-arterially delivered ethanol and Gelfoam for the treatment of severe arterioportal shunt in patients with hepatocellular carcinoma

Huang

Q²,

Jiang³

et al. 2004

WJG

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AIM:To evaluate long-term effect of ethanol embolization for the treatment of hepatocellular carcinoma (HCC) with severe hepatic arterioportal shunt (APS), compared with Gelfoam embolization. METHODS:Sixty-four patients (ethanol group) and 33 patients (Gelfoam group) with HCC and APS were respectively treated with ethanol and Gelfoam for APS before the routine interventional treatment for the tumor. Frequency of recanalization of shunt, complete occlusion of the shunt, side effects, complications, and survival rates were analyzed between the two groups. RESULTS:The occlusion rate of APS after initial treatment in ethanol group was 70.3%(45/64), and recanalization rate of 1 month after embolization was 17.8%(8/45), and complete occlusion rate was 82.8%(53/64). Those in Gelfoam group were 63.6%(21/33), 85.7%(18/21), and 18.2%(6/33). There were significant differences in recanalization rate and complete occlusion rate between the two groups (P<0.05). The survival rates in ethanol group were 78% at 6 months, 49% at 12 months, 25% at 24 months, whereas those in Gelfoam group were 58% at 6 months, 23% at 12 months, 15% at 24 months. The ethanol group showed significantly better survival than Gelfoam group (P<0.05). In the ethanol group, there was a significant prolongation of survival in patients with monofocal HCC (P<0.05) and Child class A (P<0.05). There were no significant differences in survival rate in the Gelfoam group with regard to the number of tumor and Child class (P>0.05). The incidence rate of abdominal pain during procedure in ethanol group was 82.8%. There was no significant difference in postembolization syndromes between two groups. Procedure-related hepatic failure did not occur in ethanol group. CONCLUSION:Ethanol embolization for patients with HCC and severe APS is efficacious and safe, and may contribute to prolongation of the life span versus Gelfoam embolization.Huang MS, Lin Q, Jiang ZB, Zhu KS, Guan SH, Li ZR, Shan H. Comparison of long-term effects between intra-arterially delivered ethanol and Gelfoam for the treatment of severe arterioportal shunt in patients with hepatocellular carcinoma.

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Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma

Cited by 32 publications

References 20 publications

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes

Comparison of long-term effects between intra-arterially delivered ethanol and Gelfoam for the treatment of severe arterioportal shunt in patients with hepatocellular carcinoma

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