Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial

Abstract

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.Results: Forty-six study participants (mean age, 71.2 years 6 10.2; six women and 40 men) were included; 44 participants underwent at least one TACE session. The 6-month ORR was 52% (23 of 44). The best ORR achieved was 68% (30 of 44). Fourteen of 44 (32%) participants underwent a curative treatment after TACE. Median progression-free survival, time to progression, and overall survival were 6.6 months, 9.5 months, and 18.6 months, respectively. TACE was discontinued for toxicity in four of 44 (9%) participants. The most frequent grade 3-4 adverse events were elevated aspartate aminotransferase (14 of 44, 32%), elevated g-glutamyl transpeptidase (eight of 44, 18%), hyperbilirubinemia (seven of 44, 16%), elevated alanine aminotransferase (seven of 44, 16%), and pain (seven of 44, 16%). Conclusion: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.

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

“…Doxorubicin is the most used drug in DEE-TACE, however the efficacy of the drug has been questioned (153,162), especially in a hypoxic milieu (161) and recently idarubicin has undergone initial clinical evaluation with promising results regarding safety and response (217). It is essential that a drug used in TACE have beneficial intratumoral pharmacokinetics and is effective under hypoxic conditions (218)(219)(220).…”

Integrative analysis identifies key mRNA biomarkers for diagnosis, prognosis, and therapeutic targets of HCV-associated hepatocellular carcinoma

“…We found that four of the hub genes (TOP2A, AURKA, NEK2, and RACGAP1) can serve as tumor therapeutic targets for drugs approved by FDA. Specifically, a set of TOP2A inhibitors were determined as potential chemoprotective drugs in various types of cancer, such as doxorubicin in solid tumors, leukemias and lymphomas [ 43 ], Idarubicin in HCC [ 44 ], acute myelogenous leukemia, advanced breast cancer, multiple myelom, non-Hodgkin's lymphoma, and other malignancies [ 45 ], and etoposide in several malignant tumors [ 46 – 50 ] and metastatic tumors (such as brain metastasis of breast cancer) [ 51 , 52 ]. Next, we identified candidate herbs and their effective components that may have an inhibitory impact on tumor progression via three hub genes (TOP2A, NUF2, and CCNB2).…”

Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time

“…However, a 40% biodisponibility of idarubicin was published after intra-arterial administration of idarubicin-TACE, thereby suggesting a favorable extraction ratio [ 32 ]. Idarubicin has been widely explored for IA treatment, either combined with lipiodol [ 33 ] or with drug-eluting beads [ 29 , 31 ]. In addition to these chemotherapies, we also tested lipiodol, one of the available vectors for intra-arterial therapy.…”

“…They tested 11 drugs in vitro on 3 different cell lines and showed that the most frequently-used drug for TACE in HCC (i.e., doxorubicin) was not the best candidate compared with idarubicin, which displayed the greatest cytotoxicity profile [ 27 ]. The same group conducted further clinical studies showing promising results with idarubicin [ 28 , 29 , 30 , 31 ].…”