Pharmacokinetics and toxicity of intraarterial Adriamycin for hepatocellular carcinoma: Effect of coadministration of lipiodol

Johnson, Philip J.; Kalaycı, Cem; Dobbs, Nicola; Raby, Nigel; Metivier, Elizabeth M.; Summers, Linda; Harper, P.; Williams, Roger

doi:10.1016/0168-8278(91)90873-a

Cited by 91 publications

(35 citation statements)

References 34 publications

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“…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]. 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.…”

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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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: 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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“…Despite this interventional liver-directed therapy, a residual high concentration of cytotoxic agent is found in the systemic circulation, which leads to important side effects [6]. The side effects of TACE procedures include those of the chemotherapeutic agent [7,8] and the complications of arterial embolization [9].…”

Section: Introductionmentioning

confidence: 99%

A Randomized Phase II Study of Drug-Eluting Beads versus Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma

Malenstein¹,

et al. 2011

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Background: Transcatheter arterial chemoembolization (TACE) is the standard treatment in selected patients with unresectable hepatocellular carcinoma (HCC). Drug-eluting particles are developed to reduce side effects and improve efficacy. We present safety data of a prospective randomized phase II study with doxorubicin-eluting superabsorbent polymer (SAP) microspheres. Material and Methods: We prospectively included 30 HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages (A = 3, B = 19, C = 8) and randomly assigned them to receive conventional TACE (n = 14) (control group) or doxorubicin-eluting SAP microspheres (n = 16). The doxorubicin plasma level was assessed at different time points, biochemical analysis was performed, and side effects were reported following the Common Toxicity Criteria. Tumor response was assessed at 6 weeks according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: There was a significantly lower plasma peak concentration (Cmax) of doxorubicin and smaller area under the curve (AUC) with SAP microspheres (mean Cmax 495 ± 293.9 ng/ml, mean AUC 69.7 ± 26.9 ng/ml min) compared to controls (mean Cmax 1,928 ± 560.8 ng/ml, mean AUC 165 ± 32.3 ng/ml/min; both p < 0.001). Furthermore, there were less grade 3 and no grade 4 adverse events in the SAP microsphere group. Tumor response was comparable between the groups. Conclusions: TACE with SAP microspheres leads to low plasma levels of the cytotoxic drug and therefore minimizes toxicity compared to conventional TACE.

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“…In HCC patients, it has been shown that when doxorubicin is dosed intra-arterially (without any subsequent embolization procedure), the pharmacokinetics is very similar to that of the intravenously dosed drug [84]. In other words, the drug disappearance profiles obtained from intra-arterial and intravenous administrations were similar.…”

Section: Systemic Administrationmentioning

confidence: 97%

The Roles of Doxorubicin in Hepatocellular Carcinoma

Tam¹

2013

ADMET DMPK

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Pharmacokinetics and toxicity of intraarterial Adriamycin for hepatocellular carcinoma: Effect of coadministration of lipiodol

Cited by 91 publications

References 34 publications

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

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

A Randomized Phase II Study of Drug-Eluting Beads versus Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma

The Roles of Doxorubicin in Hepatocellular Carcinoma

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