Hepatocellular carcinoma (HCC)is a globalhealthcare problem, with a high prevalence in nonindustrialized countries anda rising incidence in industrializedcountries. Sorafenib demonstrated its efficacy as the first therapeutic agent for unresectable HCC in 2007. Since then, other multitarget tyrosine kinase inhibitors have demonstrated efficacy in HCC patients. Still, the tolerabilityofthesedrugsremainsanunsolvedproblem, with 5-20% of patients permanently discontinuing their therapies due to adverse events. Donafenib is a deuterated form of sorafenib exploiting the increased bioavailability derived from the deuterium-for-hydrogen replacement. In the multicenter, randomized, controlled phase II-III trial ZGDH3, donafenib outperformed sorafenib in terms of overall survival, with favorable safety and tolerability. As a result, donafenib was approved as a possible first-line treatment of unresectable HCC by the National Medical Products Administration (NMPA) of China in 2021. In this monograph, we review the main preclinical and clinical evidence that emerged in the trials of donafenib.
Chen R., Ielasi L., di Carlo A., Tovoli F. (2023). Donafenib in hepatocellular carcinoma. DRUGS OF TODAY, 59(2), 83-90 [10.1358/dot.2023.59.2.3507751].
Donafenib in hepatocellular carcinoma
Chen R.;Ielasi L.;Tovoli F.
2023
Abstract
Hepatocellular carcinoma (HCC)is a globalhealthcare problem, with a high prevalence in nonindustrialized countries anda rising incidence in industrializedcountries. Sorafenib demonstrated its efficacy as the first therapeutic agent for unresectable HCC in 2007. Since then, other multitarget tyrosine kinase inhibitors have demonstrated efficacy in HCC patients. Still, the tolerabilityofthesedrugsremainsanunsolvedproblem, with 5-20% of patients permanently discontinuing their therapies due to adverse events. Donafenib is a deuterated form of sorafenib exploiting the increased bioavailability derived from the deuterium-for-hydrogen replacement. In the multicenter, randomized, controlled phase II-III trial ZGDH3, donafenib outperformed sorafenib in terms of overall survival, with favorable safety and tolerability. As a result, donafenib was approved as a possible first-line treatment of unresectable HCC by the National Medical Products Administration (NMPA) of China in 2021. In this monograph, we review the main preclinical and clinical evidence that emerged in the trials of donafenib.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
