Scientific background. Transarterial chemoembolization (TACE) is the treatment of choice for the intermediate stage hepatocellular carcinoma (HCC). The most used chemotherapeutic agent in TACE is doxorubicin, although there is no evidence of its greater efficacy compared to other chemotherapeutic agents. In vitro screening has suggested that anthracycline idarubicin is the most cytotoxic against HCC.
Aim and hypothesis. This doctoral thesis aims to investigate safety and efficacy of idarubicin use in TACE for the treatment of HCC. Our hypothesis is that TACE with idarubicin is safe and efficient method of treatment of HCC.
Patients and methods. Between September 2019 and December 2021, 31 intermediate stage HCC patients were included to this prospective monocentric study. A mixture of 100 m microspheres and 10 mg of idarubicin was used for treatment in all patients. Patients' clinical status and laboratory results were monitored, and follow-up imaging reviewed. The adverse events, objective response rate (ORR), progression free survival (PFS), time to TACE untreatable progression (TTUP), overall survival (OS), and pharmacokinetics were evaluated.
Results. A total of 68 procedures were performed. Grade ≥ 3 adverse events were noted in 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). For idarubicin and idarubicinol, median time to maximal plasma concentration (Tmax) were 5 min (range: 5 – 15 min) and 10 hours (range: 2 – 24 hours); mean maximal plasma concentration (Cmax) were 9.1 ± 5.0 ng/mL and 3.7 ± 1.6 ng/mL; mean area under the curve (AUC0-72) were 54.0 ± 25.8 ng/mL*h and 179.7 ± 81.4 ng/mL*h, respectively. Significant differences between patients achieving objective response and those with progressive disease were observed regarding idarubicin, idarubicinol, and their combined plasma concentrations at 72 hours post-procedure (p=0.024, 0.014, and 0.014, respectively), higher plasma concentrations were observed in patients achieving objective response. The cut-off values for objective response were identified at 1.2 ng/mL and 1.29 ng/mL for idarubicinol and combined idarubicin-idarubicinol plasma concentration, respectively.
Conclusions. TACE with idarubicin is a safe and effective method of treatment for the intermediate stage HCC with low rates of adverse events alongside high tumor response, favorable 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.
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