Pharmacokinetic and Safety Study of Doxorubicin-eluting Beads in a Porcine Model of Hepatic Arterial Embolization

Lewis, Andrew L.; Taylor, Ryan W.; Hall, Brenda; Gonzalez, M. Victoria; Willis, S.; Stratford, Peter W.

doi:10.1097/01.rvi.0000228416.21560.7f

Cited by 187 publications

(134 citation statements)

References 16 publications

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“…Interestingly, drug-elution from completely-confined embolic bead displayed a qualitatively similar profile compared with that obtained using the Tapparatus set-up [28,63], and conformed to experimental observations using animal models showing continuous drug-elution for prolonged time [10].…”

Section: Accepted M Manuscriptmentioning

confidence: 49%

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Carugo

Capretto

Roy

et al. 2015

Journal of Controlled Release

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Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device, consisting of a network of interconnected microchannels, which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy-and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3 hours was equal to ~0.2 and ~0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partiallyconfined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation.

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Section: Accepted M Manuscriptmentioning

confidence: 49%

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Carugo

Capretto

Roy

et al. 2015

Journal of Controlled Release

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“…These new vehicles may offer the opportunity to implement a higher level of standardization to HCC treatment (1). Previous studies have shown that TACE with drug-eluting microspheres has an improved pharmacokinetic profile and results in effective tumor killing in both preclinical animal models and clinical studies in humans (4)(5)(6)(7)(8). The PRECISION V randomized trial did not reach its primary end point of improved objective response at 6 months, but did identify relative benefit of using drugeluting microspheres to achieve a higher response rate in high-risk patients and lower toxicity overall (8).…”

Section: Methodsmentioning

confidence: 99%

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion

Duan¹,

Wang²,

Lam³

et al. 2016

Radiology

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q RSNA, 2015 Purpose:To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drugeluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. Materials and Methods:From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or postresection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. Results:Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. Conclusion:Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.q RSNA, 2015

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“…These beads prolong drug delivery time and decrease systemic toxicity [12][13][14]. DEB treatment can potentially enhance the therapeutic efficacy of regional, liver-directed transcatheter chemoembolization for patients with unresectable HCC by drawing on the slower, more consistent drug delivery process.…”

Section: Introductionmentioning

confidence: 99%

Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC)

Dhanasekaran

Kooby

Staley

et al. 2010

Journal of Surgical Oncology

193

149

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Background and Objectives: Chemoembolization with doxorubicin drug eluting beads (DEB) is a novel locoregional treatment modality for unresectable hepatocellular carcinoma (HCC). Initial animal studies and clinical trials suggest that treatment with DEB may provide safer and more effective short-term outcomes than conventional chemoembolization. Current study explores long-term survival benefits. Methods: Consecutive patients who received transcatheter therapy with DEB or conventional chemoembolization as sole therapy between 1998 and 2008 were studied. Statistical analysis was performed using Kaplan-Meier estimator with log-rank testing, chi-squared, and independent t-tests. Results: Seventy-one patients were included in this study, 45 (63.4%) received therapy with DEB (group A) and 26 (36.6%) underwent conventional chemoembolization (group B). Median survival from diagnosis of HCC in groups A and B were 610 (351-868) and 284 days (4-563; P ¼ 0.03), respectively. In Okuda stage I, survival in groups A and B were 501 (421-528) and 354 days (148-560, P ¼ 0.02). In Child-Pugh classes A and B, survival in groups A and B were 641 (471-810) and 323 days (161-485, P ¼ 0.002). Median survival in patients with Cancer of Liver Italian Program (CLIP) score 3 in groups A and B were 469 (358-581) and 373 days (195-551, P ¼ 0.03). NCI CTCAEv3 Grade 5 clinical toxicity was similar. Conclusions: In our study, transcatheter therapy with DEB offers a survival advantage over conventional chemoembolization for patients with unresectable HCC.

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Pharmacokinetic and Safety Study of Doxorubicin-eluting Beads in a Porcine Model of Hepatic Arterial Embolization

Cited by 187 publications

References 16 publications

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion

Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC)

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