Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma: Study of Midterm Doxorubicin Delivery in Resected Liver Specimens

D'inca, Hadrien; Piot, Olivier; Diébold, Marie-Danièle; Piardi, Tullio; Marcus, C.; Burde, Frédéric; Sommacale, Danièle; Manfait, Michel; Thiéfin, Gérard

doi:10.1016/j.jvir.2017.01.018

Cited by 8 publications

(11 citation statements)

References 15 publications

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“…The best descriptive simulations for the human data showed around 32% release. A prolonged release from DEBDOX is in agreement with in vivo studies for DOX left in DEBDOX in situ (42)(43)(44). For instance, in pigs, measurable concentrations of DOX in DEBDOX were measurable up to 90 days, although the concentration DOX in DEBDOX decreases over time (43).…”

Section: Debdoxsupporting

confidence: 83%

“…Interestingly, the in vitro release parameter estimates further suggested that it would take 77 h for 90% release from the DEB12 data set. However, a complete in vivo release is not obtained after 77 h; DEBDOX still can contain up to 42.9% of the loaded dose as long as 80 days after administration (42). This difference in extent of release might be explained by the difference in in vitro and in vivo models.…”

Section: Debdoxmentioning

confidence: 98%

“…In vivo, the dispersion or clustering of individual DEBDOX beads in the blood vessel affects the release of DOX. DEBDOX clusters with more than 10 DC beads have a 10to 20-fold higher remaining percentage than clusters with fewer beads (42). In vitro, this clustering and the effect on release have not been specifically investigated.…”

Section: Debdoxmentioning

confidence: 99%

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Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment

Dubbelboer

Sjögren

Lennernäs

2018

AAPS J

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It is important to be able to simulate and predict formulation effects on the pharmacokinetics of a drug in order to optimize effectivity in clinical practice and drug development. Two formulations containing doxorubicin are used in the treatment of hepatocellular carcinoma (HCC): a Lipiodol-based emulsion (LIPDOX) and a loadable microbead system (DEBDOX). Although equally effective, the formulations are vastly different, and little is known about the parameters affecting doxorubicin release in vivo. However, mathematical modeling can be used to predict doxorubicin release properties from these formulations and its in vivo pharmacokinetic (PK) profiles. A porcine semi-physiologically based pharmacokinetic (PBPK) model was scaled to a human physiologically based biopharmaceutical (PBBP) model that was altered to include HCC. DOX in vitro and in vivo release data from LIPDOX or DEBDOX were collected from the literature and combined with these in silico models. The simulated pharmacokinetic profiles were then compared with observed porcine and human HCC patient data. DOX pharmacokinetic profiles of LIPDOX-treated HCC patients were best predicted from release data sets acquired by in vitro methods that did not use a diffusion barrier. For the DEBDOX group, the best predictions were from the in vitro release method with a low ion concentration and a reduced loading dose. The in silico modeling combined with historical release data was effective in predicting in vivo plasma exposure. This can give useful insights into the release method properties necessary for correct in vivo predictions of pharmacokinetic profiles of HCC patients dosed with LIPDOX or DEBDOX.

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Section: Debdoxsupporting

confidence: 83%

Section: Debdoxmentioning

confidence: 98%

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Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment

Dubbelboer

Sjögren

Lennernäs

2018

AAPS J

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“…Furthermore, in vivo release is affected not only by bead size and drug loading, which are factors known to have an effect on the in vitro release rate. For example, in vivo release is also affected by clustering of the beads in the arteries, with a decrease in the percentage of DOX released as the number of beads in a cluster increases . The handling of the drug formulation before administration could also affect drug release, as mixing with ion-containing solutions (such as saline) could start the release of DOX from DEBDOX prior to administration.…”

Section: Safety and Efficacymentioning

confidence: 99%

Reply to “Comment on ‘In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma’”

et al. 2017

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“…Although conventional transarterial chemoembolization (C-TACE) using emulsions of lipiodol and chemotherapeutic agent(s) has been found to improve survival rate in patients with unresectable hepatocellular carcinoma (HCC) [1,2], this method has important drawbacks associated with techniques and scheduling, which have not yet been standardized [3]. Drug-eluting bead TACE (DEB-TACE) has several advantages over C-TACE, such as the delivery of higher concentrations of chemotherapeutic agents directly to tumors, lower rates of systemic complications, greater efficacy in advanced stage or large tumors, and better standardization of the procedure itself [4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Initial Transarterial Chemoembolization (TACE) Using HepaSpheres 20–40 µm and Subsequent Lipiodol TACE in Patients with Hepatocellular Carcinoma > 5 cm

Cho

Chu

Kim

et al. 2021

Life

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To investigate clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) using HepaSpheres 20–40 µm in diameter and subsequent cisplatin-based lipiodol TACE (Cis-TACE) in patients with hepatocellular carcinoma (HCC) > 5 cm. Materials and Methods: This study included 39 consecutive patients (34 men, 5 women; mean age, 63.5 years; range, 39–80 years) who underwent DEB-TACE using HepaSpheres 20–40 µm as first-line treatment for HCC > 5 cm (mean diameter, 8.2 cm; range, 5.1–13 cm) between September 2018 and August 2019. Patients with new tumors, residual tumors, or tumor growth after initial DEB-TACE underwent subsequent Cis-TACE. Results: All 39 patients underwent initial DEB-TACE successfully, with 35 (89.7%) and three (7.7%) patients experiencing minor and major complications, respectively. After initial DEB-TACE, one patient (2.6%) achieved complete response (CR), 35 (89.7%) achieved partial response (PR), and three (7.7%) experienced progressive disease (PD). During a median follow-up period of 14.4 months (range, 0.6–23 months), 23 patients underwent Cis-TACE, with 11, three, and nine achieving CR, PR, and PD, respectively. The median overall survival time was 20.9 months (95% confidence interval (CI), 18.6−23.2 months), the median time to progression was 8.8 months (95% CI, 6.5−11.1 months), and the median time to local tumor recurrence was 16 months (95% CI, 7.4–24.6 months). Conclusions: DEB-TACE using HepaSpheres 20–40 µm in diameter can be a safe and effective initial treatment method in patients with HCC > 5 cm. Subsequent Cis-TACE constitutes a good adjuvant method to enhance tumor response after initial DEB-TACE.

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Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma: Study of Midterm Doxorubicin Delivery in Resected Liver Specimens

Cited by 8 publications

References 15 publications

Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment

Porcine and Human In Vivo Simulations for Doxorubicin-Containing Formulations Used in Locoregional Hepatocellular Carcinoma Treatment

Reply to “Comment on ‘In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma’”

Initial Transarterial Chemoembolization (TACE) Using HepaSpheres 20–40 µm and Subsequent Lipiodol TACE in Patients with Hepatocellular Carcinoma > 5 cm

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