Idarubicin-Loaded ONCOZENE Drug-Eluting Embolic Agents for Chemoembolization of Hepatocellular Carcinoma: In Vitro Loading and Release and In Vivo Pharmacokinetics

Improved stability of lipiodol–drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin

“…Immediately after injection of the emulsion, we did not detect any idarubicin in the plasma; it took at least a few minutes for the drug to appear. When compared with data in the literature, our findings highlighted the improved PK profile of idarubicin c-TACE compared with both doxorubicin c-TACE (mean C max 10 times lower [7]) and idarubicin IV injection (mean AUC 0-24h three times lower [33]), and also showed that the in vivo release of idarubicin from a lipiodol-based emulsion was very close to that observed from DEEs [23,34] (Table 4). The first peak of idarubicinol concentration between 5 and 10 min after injection of the emulsion can be explained by the very quick extraction of part of the idarubicin by hepatocytes followed by its immediate metabolisation.…”

“…Only eight patients were included in the PK analysis. It was not possible to characterise fully idarubicinol PK since its half-life is long, and we did not collect any blood samples after 24 h. However, the standard deviation values of both C max and AUC 0-24h in the present study were as tight as those reported with idarubicin-loaded DEEs [23,34]. For further optimisation of idarubicin-lipiodol therapy, and besides the PK characteristics in serum, the distribution of the drug and its metabolite within the liver must be explored through histopathological studies, such as the one by Namur et al, who demonstrated that doxorubicin concentrations achieved around the doxorubicin-eluting embolics were high enough to induce antiproliferative and cytotoxic effects on the tumour cells surrounding the DEEs [36].…”

Transarterial chemoembolization for hepatocellular carcinoma: An old method, now flavor of the day

“…The maximum tolerated dose of 10 mg of idarubicin was established during a phase I study with loadable microspheres [23]. Its efficacy and tolerability have since been demonstrated at this dose for Lipiodol ® conventional TACE [24,25] or with other loaded microspheres [26] in patients with ioperable HCC. Once phase II multicenter study is currently ongoing to assess the long term efficacy-tolerability profile of TACE using microspheres loaded with idarubicin in patients with inoperable HCC (study FFCD1307-IDASPHERE II).…”

“…Microspheres have advantages over Lipiodol ® : loading is standardized in pharmacies whereas extemporaneous preparation of a Lipiodol ® emulsion is still very empirical; the particles are poorly deformable and the calibrated size enables the operator to select the size of vessels to be embolized. Very recent studies have shown small microspheres (≤ 100 m) to be of particular benefit as they cause more distal embolization [26,[32][33][34]. More severe hepatic and biliary toxicity, however, has also been found for the microspheres compared to Lipiodol ® [35,36].…”

Chimioembolisation des carcinomes hépatocellulaires : une vieille méthode au goût du jour

“…La dose maximale tolérée de 10 mg d'idarubicine a été déterminée au cours d'un essai de phase I avec des microsphères chargeables [23]. Son efficacité et sa tolérance ont depuis été démontrées à cette dose pour la CHE lipiodolée [24,25] ou avec d'autres microsphères chargées [26] chez des patients atteints d'un CHC non résécable. Une étude de phase multicentrique de phase II est actuellement en cours et vise à évaluer le profil efficacité-tolérance au long cours d'un traitement par CHE avec microsphères chargées d'idarubicine chez des patients atteints d'un CHC non résécable (essai FFCD1307-IDASPHERE II).…”