Safety and efficacy of intra-arterial hepatic chemotherapy with doxorubicin-loaded nanoparticles in hepatocellular carcinoma.

ESMO Open
Philippe MerlePierre Attali

Abstract

Doxorubicin Transdrug (DT), a nanoformulation of doxorubicin, was demonstrated to overcome the chemoresistance of hepatocellular carcinoma (HCC) in preclinical models. Its efficacy and safety were thus investigated in phase I and randomised phase II trials in unresectable HCC. Phase I was a single dose of DT through the hepatic intra-arterial (HIA) route, dose-escalating 3+3 trial, evaluating five-dose levels from 10 to 40 mg/m2 with maximal tolerated dose (MTD) as primary endpoint. The multicentre phase II trial randomly assigned (2:1 ratio) patients to receive either 30 mg/m2 of DT through HIA route every 4 weeks for up to three courses or best standard of care (BSC). Progression-free survival (PFS) rate at 3 months was the primary endpoint. Overall survival (OS) and disease control rate (DCR) were secondary endpoints. In phase I, haematological and respiratory limited toxicities were reported at 35 and 40 mg/m2, giving MTD at 30 mg/m2. Partial response rate was 10%, and stable disease 70%. Phase II was discontinued due to three severe acute respiratory distress events in the DT group while 17 patients had received 30 mg/m2 DT and 11 BSC. At 3 months, PFS was 64% (95% CI 31 to 89) vs 75% (95% CI 35 to 97), and DCR 35% vs 27% ...Continue Reading

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Citations

Feb 6, 2019·Journal of Drug Targeting·Simona MuraJulien Nicolas
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Jun 25, 2019·ESMO Open·Christoph C Zielinski
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Jun 20, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Roman KloecknerJordi Bruix
May 23, 2019·Cancer Immunology Research·Zhen TaoKe Chen
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Feb 23, 2021·Frontiers in Pharmacology·Agnese GagliardiDonato Cosco
Oct 3, 2021·International Journal of Pharmaceutics·Christelle ZandanelChristine Vauthier

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