The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.

Idarubicin-eluting beads showed a good safety profile and promising objective response rate and time to progression when used as part of a transarterial chemoembolization regimen for unresectable hepatocellular carcinoma. BackgroundA prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study.PurposeTo evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC.Materials and MethodsThis prospective single-arm phase II study was conducted between January 2015 and January 2017. Participants with unresectable HCC were included in the trial and underwent TACE with idarubicin-eluting beads. The primary end point was 6-month ORR assessed with independent central review by using modified Response Evaluation Criteria in Solid Tumors. Secondary end points were best ORR during the first 6 months, overall survival, progression-free survival, time to progression, and safety. A two-stage Fleming statistical design was used.ResultsForty-six study participants (me...

Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3–10) in the citrate group and 5 days (IQR 3–11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin. In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated. Postembolization syndrome was observed after 30.9 % (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3–5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19 % (4 of 21) of patients. On imaging, no progression was encountered; four patients (24 %) exhibited stable disease, 12 (57 %) exhibited a partial response, and five (19 %) exhibited a complete response. Median TTTF was 16.7 months (Kaplan–Meier analysis). At 6 months, 94.7 % (95 % confidence interval [CI] 68.1–99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6 % (95 % CI 21.6–73.9) of patients at 1 year. Overall survival was 83.5 % (95 % CI 57–94.4) at 1 year. Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.

Objective: To describe the responses, toxicities and outcomes of HCC patients treated by transarterial chemoembolization (TACE) using idarubicin-loaded TANDEM beads. Materials and Methods: Seventy-two consecutive patients (mean age: 71 years (58–84 years)) with HCC were treated by TACE using idarubicin-loaded TANDEM in a first line, over a five-year period. Most patients (89%) had liver cirrhosis classified as Child–Pugh A (90%). BCLC B classification applied in 85% of cases. Baseline tumor burden was limited to one to three nodules in 92% of cases, unilobar in 88% cases, with a median tumor diameter of 55 mm (range: 13–150 mm). Toxicity was assessed using NCI CTC AE v4.0. Response was assessed using mRECIST criteria. Time-to-treatment failure (TTTF) and overall survival (OS) were also calculated based on Kaplan–Meier method. Result: Of 141 TACE sessions performed with bead sizes of 100 and 75 µm in 42 (29.8%) and 99 (70.2%) sessions, respectively. In 78% of all TACE sessions, the full dose of idarubicin-loaded beads was injected. Grade 3–4 AE were observed after 73 (52%) sessions, most of them being biological. Multi-organ failure was observed three days after the first TACE in a Child B patients, unfortunately leading to death. Overall, the best objective response rate (ORR) was 65%. Median follow-up lasted 14.3 months (95% CI: 11.2–18.8 months). Median TTTF and OS were 14.4 months (95% CI: 7.2–24.6 months) and 34.6 months (95% CI: 24.7—not reached) respectively. Conclusion: In this retrospective study involving well-selected HCC patients, high ORR and long TTTF and OS are observed after TACE using idarubicin-loaded TANDEM. A randomized trial is needed.