Drug-eluting Transarterial Chemoembolization Research Articles

Explosomes: A new modality for DEB-TACE local delivery of sorafenib: In vivo proof of sustained release

The current medical practice in treating Hepatocellular carcinoma (HCC) using Drug Eluting Transarterial chemoembolization (DEB-TACE) technique is limited only to hydrophilic ionizable drugs, that can be attached ionically to the oppositely charged beads. This limitation has forced physicians to subscribe the more hydrophobic, first treatment option drugs, like sorafenib systemically via the oral route, thus flooding the patient system with a very powerful, non-specific, multiple-receptor tyrosine kinase inhibitor that is associated with notorious side effects. In this paper, a new modality is introduced, where highly charged, drug loaded liposomes are added to oppositely charged DEBs in a manner causing them to “explode” and the drug is eventually attached to the beads in the lipid patches covering their surfaces; therefore we call them “Explosomes”. After fully describing the preparation process and in vitro characterization, this manuscript delves into an in vivo pharmacokinetic study over 50 New Zealand rabbits, where explosomal loading is challenged vs oral as well as current practice of emulsifying sorafenib in lipiodol. Over 14 days of follow up, and compared to other groups, explosomal loading of SRF on embolic beads proved to cause a slower release pattern with longer Tmax, lower Cmax and less washout to general circulation in healthy animals. This treatment modality opens a new untapped door for local sustained delivery of hydrophobic drugs in catheterized organs.

Transarterial chemoembolization of hepatocellular carcinoma

Transarterial chemoembolization (TACE) is used as palliative and neoadjuvant treatment for patients with hepatocellular carcinoma (HCC). TACE should be offered as palliative treatment to patients with intermediate stage large or multinodular HCC if no curative treatment option is available by resection or thermoablation and if extrahepatic metastases and tumor infiltration of main portal and systemic veins has been excluded. TACE is possible only in patients with preserved liver function (Child-PughA-B, best up to 7points) and with good performance status (ECOG0). TACE can be used for bridging and for downstaging prior to liver transplantation with the intention to maintain or reach limited intrahepatic tumor load defined by Milan criteria. TACE should be adapted to the vascularization pattern of the HCC nodules and performed as selective as possible and repetetively if necessary with the goal of complete devascularization of the tumor tissue. Conventional TACE (cytotoxic drugs, iodized oil and embolic particles) and drug-eluting TACE (anthracycline preloaded in microspheres) can be used in acomparable way. During drug-eluting TACE, peripheral concentration of cytotoxic drugs is lower. Using conventional TACE in apalliative setting, survival benefit for patients was 8-11months compared to best supportive care; however, this requires that all known contraindications and other criteria in terms of tumor and liver disease, respectively, associated with negative prognosis be taken into consideration. Better local response is achieved by drug-eluting TACE; however, no related survival benefit was shown compared to conventional TACE so far. Response to neoadjuvant local treatment is associated with improved prognosis after liver transplantation.

Advances in regional chemotherapy of the liver

Introduction: Primary and secondary liver tumors resemble some of the most common causes of cancer and represent a major clinical problem owing to the poor prognosis. First-line therapeutic concepts are mainly based on surgical resection and/or systemic chemotherapy (SCT). However, many patients are not suitable for surgery or have failed SCT, although the total tumor load is still limited, which makes a regional therapy approach appealing.Areas covered: This review focuses on different types of transarterial instillation of chemotherapy, which encompasses conventional and drug-eluting transarterial chemoembolization (TACE), hepatic arterial infusion (HAI) chemotherapy and isolated hepatic perfusion (ILP).Expert opinion: TACE can be regarded as the treatment of choice in patients with multinodular hepatocellular carcinoma, but it should still be performed as a lipiodol-based regimen, while the value of doxorubicin-eluting beads needs to be exploited in further randomized controlled trials (RCTs). For patients with colorectal liver metastases, HAI chemotherapy has been challenged by the advent of more effective SCT, but encouraging results have been observed for the combination of the most recent, active drugs given by means of HAI with SCT. Nevertheless, data from RCTs comparing SCT with this transarterial regional therapy approach, as well as with TACE and ILP, are urgently needed.