Drug-eluting Microspheres Research Articles

Idarubicin-loaded drug-eluting microspheres transarterial chemoembolization for intermediate stage hepatocellular carcinoma: safety, efficacy, and pharmacokinetics.

Transarterial chemoembolization (TACE) is the treatment of choice for the intermediate stage hepatocellular carcinoma (HCC). Doxorubicin remains the most used chemotherapeutic agent in TACE, although in vitro screening has demonstrated that idarubicin exhibits greater cytotoxicity against HCC. This study aimed to evaluate safety, efficacy, and pharmacokinetics of idarubicin-loaded drug-eluting microspheres TACE (DEMIDA-TACE) in intermediate stage HCC patients. Between September 2019 and December 2021, 31 consecutive intermediate stage HCC patients (96.8% cirrhotic) were included to this study. 2 mL of LifePearl™ microspheres (100 μm) loaded with 10 mg of 1 mg/mL idarubicin were used for treatment. The adverse events, objective response rate (ORR), progression free survival (PFS), time to TACE untreatable progression (TTUP), median overall survival (mOS), and pharmacokinetics were evaluated. There were 68 TACE procedures performed. Adverse events grade ≥ 3 were noted after 29.4% procedures. The ORR was 83.9%, median PFS and TTUP were 10.5 months (95% CI: 6.8-14.3 months) and 24.6 months (95% CI: 11.6-37.6 months), respectively. Median OS was 36.0 months (95% CI: 21.1-50.9 months). Significant differences between patients achieving objective response (OR) and those with progressive disease were observed regarding idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure, higher plasma concentrations were observed in patients achieving OR (p = 0.014 and 0.014; cut-off values 1.2 and 1.29 ng/mL, respectively). DEMIDA-TACE emerges as a safe and effective method of treatment for the intermediate stage HCC with low rates of adverse events alongside high tumor response, favourable disease control and overall survival. Idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure may serve as prognostic factors for achieving OR.

A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy.

Drug-eluting bead transcatheter arterial chemoembolization (D-TACE) is one of the first-line treatment for intermediate hepatocellular carcinoma (HCC). However, the dual hypoxia microenvironment, due to inherent tumor hypoxia and TACE-induced hypoxia, triggers drug resistance in HCC. To address this challenge, the study develops multicavitary microspheres capable of encapsulating oxygen and harnessing magnetic hyperthermia to enhance oxygen permeability. The novel multicavitary oxygen-encapsulated magnetothermal drug-eluting microspheres (OTD-Ms) effectively reduce hypoxia-related proteins (HIF-1α, VEGF-A) and drug resistance (P-gp) both in vitro and in vivo. Moreover, these microspheres demonstrate improved TACE efficacy and enhance survival rates in a rabbit VX-2 tumor model, suggesting their potential for HCC treatment.

1481P A case-control study of drug-eluting microspheres and blank microspheres in bronchial artery embolization for hemoptysis in non-small cell lung cancer

1481P A case-control study of drug-eluting microspheres and blank microspheres in bronchial artery embolization for hemoptysis in non-small cell lung cancer

Efficacy of transarterial chemoembolization treatment with 30-60-μm microspheres in patients with hepatocellular carcinoma.

Chemoembolization with small drug-eluting microspheres is widely used in the treatment of hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of transarterial chemoembolization with doxorubicin-eluting 30-60-µm microspheres (DEB-TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) stageA andB HCC. In this single-center study, 88patients with HCC (BCLC A/B: 15.9%/84.1%) who underwent 137 DEB-TACE sessions between January 2015 and December 2020 were retrospectively assessed. Response to treatment was assessed 4-8weeks after each DEB-TACE procedure according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) criteria. Progression-free survival (PFS), time to progression (TTP), overall survival (OS), and adverse events were recorded. In 88patients (84.1% males; median age, 66.0years; range, 22-83), the median follow-up was 17months (range, 2-64). Eight patients (9.1%) had acomplete response, 42 (47.8%) had partial regression, 10 (11.3%) had stable disease, and 28 (31.8%) had progressive disease. There was astatistically significant difference between serum alpha-fetoprotein (AFP) levels before and after DEB-TACE treatment (p < 0.001). The median OS was 17months (95% confidence interval [CI], 10.3-23.7). Cox regression analyses found that preprocedural serum AFP level (400+ vs. < 400; p = 0.024), Child Pugh classification (Bvs. A; p = 0.019), and number of DEB-TACE sessions (1 vs. > 1; p = 0.003) were independent risk factors affecting OS. The median PFS was 8months (95% CI, 5.8-10.2) and TTP was 6months (1-14months). Chemoembolization with 30-60-µm microspheres is an effective and safe treatment for HCC. The number of DEB-TACE sessions is also one of the factors affecting OS.

Clinical Effectiveness of Drug-Eluting Microsphere Transcatheter Arterial Chemoembolization Combined with First-Line Chemotherapy as the Initial Treatment for Patients with Unresectable Intrahepatic Cholangiocarcinoma

PurposeTo evaluate the safety and effectiveness of the combination of drug-eluting microsphere (DEM) transcatheter arterial chemoembolization (TACE) with those of chemotherapy in treating unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsSeventy patients diagnosed with unresectable ICC between January 2016 and December 2020 were retrospectively included in this study. Of these, 39 patients received DEM-TACE and first-line chemotherapy (TACE+Chemo group) and 31 received chemotherapy alone (Chemo group). Propensity score matching was performed to reduce selection bias between the TACE+Chemo and the Chemo groups. Differences in tumor response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between 2 groups. ResultsThe patients in the TACE+Chemo group had better median OS (18.6 vs 11.9 months; P = .018), median PFS (11.9 vs 6.9 months, P = .033), and objective response rates (56.8% vs 13.3%; P < .001) than those in the Chemo group. TRAEs showed a higher incidence of transient elevation of transaminase and abdominal pain in the TACE+Chemo group than in the Chemo group (P < .001). ConclusionsCompared with chemotherapy alone, DEM-TACE combined with first-line chemotherapy may be a viable and safe treatment option for unresectable ICC.

X-ray Opaque Polymer Drug-Eluting Beads Loaded with Iodized Oil: Preparation and In Vitro and In Vivo Evaluations.

Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 μm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.

Long-Term Outcomes of Balloon TACE for HCC: An European Multicentre Single-Arm Retrospective Study

PurposeTo report response rates (using mRECIST), overall survival (OS), progression-free survival and local tumour recurrence-free survival (LRFS) of balloon-occluded transarterial chemoembolisation (bTACE) for hepatocellular carcinoma (HCC).Materials and MethodsPatients from five European centres treated with conventional or drug-eluting microsphere bTACE for HCC were included, and patients already lost to follow-up before 12 months were excluded. Possible factors contributing to LRFS and OS were evaluated with Cox proportional hazards models.ResultsSeventy-three patients were enrolled. The mean number of nodules per patient was 2.07(± 1.68), and the average maximum diameter of the nodules was 37 ± 19.9 mm. The response of the target lesion at 6 months was complete response (CR) in 58.9%, partial response (PR) in 28.8%, stable disease (SD) in 6.8% and progressive disease (PD) in 5.5%. The median follow-up time was 31 months; at the last follow-up, target tumour response was CR in 49.3%, PR in 12.3%, SD in 5.5% and PD 32.9%. Overall response at the last follow-up was CR in 17.8%, PR in 9.6%, SD 2.7% and PD in 69.9% (for new lesions in 37% of patients). Median OS was not reached; mean overall survival was 50.0 months, while median LRFS was 31.0 months. At uni- and multivariable analysis, only tumour maximum diameter was related to LRFS (hazard ratio [HR] = 1.021; 95% CI 1.004–1.038, P = 0.015).ConclusionsbTACE demonstrated high efficacy for HCC, with a complete response in 58.9% of patients, a median local recurrence-free survival of 31.0 months and a mean overall survival of 50.0 months.Graphical

Celecoxib and cisplatin dual-loaded microspheres synergistically enhance transarterial chemoembolization effect of hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.

Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer

PurposeTo assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. Materials and MethodsThirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. ResultsThe local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. ConclusionTransarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

Efficiency of Transarterial Chemoembolization with Drug-Eluting Microspheres in the Treatment of Metastatic and Primary Liver Tumors

Background: Transarterial chemoembolization (TACE) is coming into use in the treatment of liver tumors, with drug-eluting microspheres as one of the technique variations. However, at the moment there are no systematic studies that would answer the questions: what is the role of the method in the treatment regimen for patients with primary and metastatic liver tumor and at what stage should it be used? Aim: to evaluate the effectiveness of transarterial chemoembolization with drug-eluting microspheres for the treatment of metastatic and primary malignant liver tumors at different stages of the disease. Methods: We performed а retrospective observational uncontrolled study of 65 patients with liver metastases (Group 1), and 10 patients with primary malignant liver tumors (Group 2), who underwent 102 operations of transarterial chemoembolization with drug-eluting microspheres. To plan transarterial chemoembolization and evaluate its effectiveness, computed tomography and magnetic resonance imaging were used every 89 weeks during the treatment. Results: After two transarterial chemoembolization controls, Group 1 included 51 responders (79%) and 14 non-responders (21%). Among the responders by the 16th week there was a decrease in the volume of the tumor mass in the liver from 12.4 [4.7; 24.6] to 5.2 cm3 [2; 15.5] for colorectal cancer, from 26 [18; 35] to 19 cm3 [13; 25] for neuroendocrine cancer, from 12 [4; 20] to 4 cm3 [0.6; 9] for adenocarcinomas of different localizations. There was no progression in Group 2, while, by week 16, there was a decrease in the tumor volume from 142 [51; 206] to 68 cm3 [23; 185] for hepatocellular carcinoma, from 465 [330; 600] to 187 cm3 [137;237] for intrahepatic cholangiocarcinoma. With repeated transarterial chemoembolization, a decrease in the volume of the tumor mass was also noted, while the time without progression decreased from 303 [170; 369] to 180 [105; 225] days in Group 1, from 266 [200; 367] to 120 [62; 215] days in Group 2. Conclusions: Transarterial chemoembolization with drug-eluting microspheres is an effective treatment for primary and metastatic liver tumors. It should be considered as a palliative therapy, which allows achieving a good antitumor response at different stages of cancer.

Mass Spectrometry Imaging of Biomaterials.

The science related to biomaterials and tissue engineering accounts for a growing part of our knowledge. Surface modifications of biomaterials, their performance in vitro, and the interaction between them and surrounding tissues are gaining more and more attention. It is because we are interested in finding sophisticated materials that help us to treat or mitigate different disorders. Therefore, efficient methods for surface analysis are needed. Several methods are routinely applied to characterize the physical and chemical properties of the biomaterial surface. Mass Spectrometry Imaging (MSI) techniques are able to measure the information about molecular composition simultaneously from biomaterial and adjacent tissue. That is why it can answer the questions connected with biomaterial characteristics and their biological influence. Moreover, this kind of analysis does not demand any antibodies or dyes that may influence the studied items. It means that we can correlate surface chemistry with a biological response without any modification that could distort the image. In our review, we presented examples of biomaterials analyzed by MSI techniques to indicate the utility of SIMS, MALDI, and DESI-three major ones in the field of biomaterials applications. Examples include biomaterials used to treat vascular system diseases, bone implants with the effects of implanted material on adjacent tissues, nanofibers and membranes monitored by mass spectrometry-related techniques, analyses of drug-eluting long-acting parenteral (LAPs) implants and microspheres where MSI serves as a quality control system.

Drug-eluting Microspheres Compared to Conventional Transarterial Chemoembolization as First Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-center Retrospective Cost-utility Analysis

PurposeTo assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy.Materials and MethodsThe economic evaluation is based on a retrospective single-center study and individual patients’ data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results.ResultsA total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p < 0.001); while mean costs were € 24,619 and € 17,001, respectively (p < 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times.ConclusionsThe higher prices of DEMs are counterbalanced by the positive impact on QALY.

Tirapazamine-loaded CalliSpheres microspheres: Preparation and characterization as a chemoembolization agent for liver cancer

Tirapazamine (TPZ), a hypoxia-selective cytotoxic agent, has proved to exert synergistic tumor-killing activity with transcatheter arterial embolization (TAE) against liver cancer. This advances TPZ to transcatheter therapies for liver cancer, particularly in combination with drug-eluting microspheres. We describe methods for preparing and characterizing TPZ-loaded CalliSpheres microspheres (CSMTPZs) with regard to their properties as a chemoembolization agent, which includes 1) preparation of CSMTPZs and determination of drug loading level, 2) in vitro determination of TPZ release, 3) assessment of CSMTPZ size and appearance, and 4) determination of TPZ pharmacokinetics and intratumoral drug concentration in vivo. These methods can be adapted for further clinical I trial.•This is to our knowledge the first methods for preparing and characterizing tirapazamine-loaded microspheres with regard to their properties as a chemoembolization agent•Detailed protocols for preparation of CSMTPZs, determination of drug loading level, in vitro determination of TPZ release, assessment of CSMTPZ size and appearance, and in vivo determination of TPZ pharmacokinetics and intratumoral drug concentration•Adaptable to experiments on other animal models and clinical trials

Retrospective Study of the Efficacy and Safety of Chemoembolization with Drug-Eluting Microspheres Combined with Intra-Arterial Infusion of Bevacizumab for Unresectable Hepatocellular Carcinoma.

PurposeTo evaluate the efficacy and safety of chemoembolization with drug-eluting microspheres (DEM-TACE) combined with intra-arterial infusion of bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC) and to identify possible prognostic factors.Patients and MethodsBetween November 2014 and December 2020, 34 patients underwent DEM-TACE combined with intra-arterial infusion of bevacizumab for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) beyond the Up-to-seven criteria or BCLC stage C HCC. Patients with extrahepatic metastasis or inferior vena cava invasion were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were safety (assessed using Common Terminology Criteria for Adverse Events v5.0), the response rate at 1 month, and the identification of prognostic factors. The median OS was calculated using the Kaplan–Meier method. The response rate was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Prognostic factors were investigated by univariate and multivariable analysis using the Cox proportional hazards model.ResultsThe median OS was 13 months. BCLC stage and presence of portal vein invasion were not significantly associated with OS. There were no grade ≥3 adverse events. The Child–Pugh class did not decline after treatment in 31 of 34 patients. The overall response rate was 14.2% and the disease control rate was 100%. Significant prognostic factors were alcoholic liver disease, Child–Pugh score of ≥8, and microsphere size of 50–100 μm.ConclusionDEM-TACE combined with intra-arterial infusion of bevacizumab is safe and effective, and it could be a treatment option for unresectable HCCs.

Safety and efficacy of drug-eluting microspheres chemoembolization under cone beam computed tomography control in patients with early and intermediate stage hepatocellular carcinoma.

BackgroundDrug-eluting microsphere transarterial chemoembolization (DEM-TACE) is the standard of care in patients with intermediate-stage hepatocellular carcinoma and ensures targeted and controlled cytotoxic and ischemic effects. Proper patient selection and optimized treatment techniques are associated with longer median survival. The aim of this single-institution retrospective study was to evaluate safety and efficacy of DEM-TACE under cone beam computed tomography (CBCT) control in patients with early and intermediate stage hepatocellular carcinoma.Patients and methodsA total of 144 patients (mean age 67.9 ± 8.0 years, 127 males and 17 females) between February 2010 and December 2018 were studied. Microparticles of different dimensions according to two manufacturers (diameter of 70–150 μm, 100–300 μm or 300–500 μm and 40-μm, 75-μm or 100-μm) were used and loaded with 50–150 mg of doxorubicin. The objective tumour response according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), the time to progression, adverse events and overall survival were (OS) evaluated.ResultsIn total, 452 procedures were performed (median, 3 per patient). Four (0.9% of all procedures) major complications were noted. Postembolization syndrome occurred after 35% of procedures. At the first imaging follow-up 2–3 months after first treatment, 91% of patients achieved an objective response. The median time to progression was 10.2 months (95% CI: 8.3-12.1 months). OS rates at 1, 2, 3, 4, and 5 years were 85%, 53%, 33%, 20% and 14%, respectively. The median survival time was 25.8 months (95% CI: 22.1–29.5 months).ConclusionsDEM-TACE under CBCT control in patients with early and intermediate stage hepatocellular carcinoma is a safe and effective method of treatment with high objective tumour response and survival rates.

Evaluation of the use of a novel bioabsorbable polymer drug-eluting microsphere for transarterial embolization of hepatocellular neoplasia in dogs.

In dogs with non-resectable hepatic neoplasia, treatment options are limited. The objectives of this study were to describe the use of a novel drug-eluting embolic microsphere containing paclitaxel for use during transarterial chemoembolization (TACE), to compare results of liver-specific owner questionnaires and tumor volume pre- and post-TACE, and to measure systemic paclitaxel concentration post-TACE. Client-owned dogs with non-resectable hepatic neoplasia were prospectively enrolled. All owners completed questionnaires validated for the assessment of subjective outcomes in dogs with cancer before the TACE procedure and approximately 4 weeks after the TACE procedure. A CT scan was performed before TACE and 1 month after TACE; results were compared. Blood samples were obtained at specified time points post-TACE to determine systemic paclitaxel concentrations. Seven dogs (median weight: 8.9 kg; range, 4.3–31 kg) were enrolled. TACE was successfully performed in all dogs, and no intra-procedural complications were encountered. Questionnaire scores improved significantly post-TACE. Among the 6 dogs for which full data were available, median pre-TACE tumor volume was 390 cc (range 152–1,484; interquartile range 231–1,139) and median post-TACE tumor volume was 203 cc (range 98–889; interquartile range 151–369), which was significantly (P = .028) lower. All 6 dogs had a reduction in volume at the post-TACE measurement. Mean percent change in tumor volume was -45.6% (95%CI -58.6 to -32.6%). The mean plasma paclitaxel concentration in canine blood peaked at 4 days post-TACE procedure and was 25.7 ng/mL (range = 3.09–110 ng/mL) Median survival time was 629 days (95%CI 18 to upper limit not reached). The use of a novel paclitaxel-eluting microsphere in this cohort of dogs successfully decreased tumor volume significantly after TACE and improved clinical signs. Future investigation into the use of TACE and other similar therapies is warranted due to the promising outcomes noted in this cohort.

Treatment Benefits and Side Effects of Transarterial Chemoembolization with Drug-Eluting Bead Microspheres (DEB-TACE) in Hepatocellular Carcinoma Patients with Conventional TACE Resistance: A Retrospective Study

Background: Hepatocellular carcinoma (HCC) is currently the fourth most common malignant tumor and the second most fatal tumor in China, posing serious threats to the health and life of individuals. Objectives: This retrospective study aimed to investigate the treatment benefits and side effects of transarterial chemoembolization with drug-eluting bead microspheres (DEB-TACE) for HCC patients with conventional TACE (cTACE) resistance. Patients and Methods: A total of 17 HCC patients with cTACE resistance, treated by DEB-TACE, were retrospectively analyzed from July 2017 to December 2019. According to the modified response evaluation criteria in solid tumors (mRECIST), the efficacy of treatment was classified into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD), and the objective remission rate (ORR) and the disease control rate (DCR) were also measured at 6 and 12 weeks post-DEB-TACE treatment. Changes in liver enzymes, routine blood tests, and alpha-fetoprotein (AFP) levels were also documented. Besides, the patients’ adverse reactions were observed within one week after surgery to assess the safety of DEB-TACE therapy. Results: In patients with cTACE resistance, the CR, PR, SD, PD, ORR, and DCR were 0, 35.29%, 47.06%, 17.65%, 35.29%, and 82.35% at six weeks after DEB-TACE and 5.88%, 47.06%, 29.41%, 17.65%, 52.94%, and 82.35% after 12 weeks, respectively. In the first week after DEB-TACE, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and white blood cells elevated temporarily (P &lt; 0.05), and side effects, such as slight pain, fever, nausea, and vomiting, occurred after surgery. Following liver protection and symptomatic treatment, the patients recovered well. Conclusion: Based on the results of this study, DEB-TACE has treatment benefits and few side effects for HCC patients with cTACE resistance.

Polyethylene Glycol Drug-Eluting Embolic Microspheres Loaded with Doxorubicin for the Treatment of Hepatocellular Carcinoma: Feasibility, Safety, and Pharmacokinetic Study

PurposePolyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC). Materials and methodsThe current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0. Patients in Cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed on the basis of the specific dose of doxorubicin that the patients received because some patients received less than the assigned dose. Patients in Cohort II received the maximum safe tested dose. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 4.03. The tumor response was evaluated every 3 months according to the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors. ResultsThe maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75–100, and 101–150 mg of doxorubicin, the peak plasma concentrations were 286.7 ng/mL ± 220.1, 157.1 ng/mL ± 94.6, and 245.4 ng/mL ± 142.8, respectively; the areas under the curves calculated from 0 to 24 h were 421.7 (ng × h)/mL ± 221.2, 288.1 (ng × h)/mL ± 100.9, and 608.3 (ng × h)/mL ± 319.3, respectively, with almost complete clearance at 24 h. There was no death within 30 d. The best objective response rate was 81%, and the disease control rate was 91%. The median overall survival was 27.2 months (95% confidence interval [CI], 17.5 months to not evaluated [n.e.]); the median progression-free survival was 9.8 months (95% CI, 5.5 months to n.e.). ConclusionsPEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.

Evaluation of immune-modulating drugs for use in drug-eluting microsphere transarterial embolization

Cancer immunotherapy has yet to reach its full potential due in part to limited response rates and side effects inherent to systemic delivery of immune-modulating drugs. Local administration of immunotherapy using drug-eluting embolic (DEE) microspheres as drug delivery vehicles for direct infusion into tumor-feeding arteries might increase and prolong tumor drug concentrations and reduce systemic drug exposure, potentially improving the risk-to-benefit ratio of these agents. The purpose of this study was to evaluate the ability of four immune modulators affecting two different immune pathways to potentiate replication of immune cells from a woodchuck model of hepatocellular carcinoma. DSR 6434, a Toll-like receptor agonist, and BMS-202, a PD-L1 checkpoint inhibitor, induced immune cell replication and were successfully loaded into radiopaque DEE microspheres in high concentrations. Release of DSR 6434 from the DEE microspheres was rapid (t99% = 0.4 h) upon submersion in a physiologic saline solution while BMS-202 demonstrated a more sustained release profile (t99% = 17.9 h). These findings demonstrate the feasibility of controlled delivery of immune-modulating drugs via a local DEE microsphere delivery paradigm.

Safety and efficacy of DEM-TACE performed with drug-eluting microspheres smaller than 300 μm in patients with HCC and TIPS

Aim: Safety and efficacy evidence of drug-eluting-microspheres trans-arterial chemoembolization (DEM-TACE) in patients with hepatocellular carcinoma (HCC) and trans-jugular intrahepatic portosystemic shunt (TIPS) is lacking. The aim of this retrospective study was to report the safety and efficacy of DEM-TACE procedures performed with microspheres smaller than 300 μm in patients with HCC and TIPS in a high-volume transplant center. Methods: Embolization was standardized by initiating DEM-TACE with microspheres smaller than 100 μm, and if stasis was not achieved, adjunctive embolization with 100-300 or 200 μm microspheres was administered. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria at 1, 3-6, 9-12, and 15-18 months. Reporting the safety profile, detailed laboratory analysis was performed before, at 36-48 h, and 30-60 days after the procedure. Adverse events (AEs) were recorded; post-embolic syndrome was defined as the onset of fever/nausea/pain after the procedure. Late onset hepatobiliary complications were evaluated by follow-up imaging with computed tomography or magnetic resonance (CT/MR). Results: From December 2007 to November 2020, 17 HCC patients (25 HCC nodules) with patent TIPS underwent 20 DEM-TACE. Embolization was performed only with microspheres smaller than 100 μm in 3/20 DEM-TACE (15%); adjunctive embolization with 100-300 or 200 μm microspheres was required in 17/20 DEM-TACE (85%). Reported early AEs were post-embolic syndrome (9/20; 45%) all of grade 1-2, late AEs were asymptomatic acute liver bile duct injury (2/20; 10%), and in one case we observed hepatic abscess (1/20; 5%) resulting in death due to sepsis. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria. Complete response (CR) at 1, 3-6, 9-12, and 15-18 months was 52%, 50%, 50%, and 50%, respectively. Objective response (CR + partial response) at 1, 3-6, 9-12, and 15-18 months was 95%, 71%, 70%, and 50%, respectively. Conclusion: DEM-TACE with drug-eluting-microspheres smaller than 300 μm can be performed in appropriately selected patients with TIPS.