Discordance Between Child-Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds.

Discordance Between Child-Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds. J Clin Pharmacol. 2020 Jul 20;: Authors: Elmeliegy M, Yang DZ, Salama E, Parivar K, Wang DD Abstract Guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency recommends using Child-Pugh classification for pharmacokinetic evaluation in noncancer subjects with hepatic impairment (HI). Therefore, dosing recommendations for oncology compounds for patients with HI are commonly based on Child-Pugh classification. In oncology clinical practice, National Cancer Institute classification (NCIc), is commonly used for evaluating hepatic function and dosing decisions for oncology patients. This work evaluated the discordance between the 2 systems and the impact on dosing recommendations. The classification system in HI studies was reviewed for FDA-approved oncology compounds. Discordance between Child-Pugh and NCIc was evaluated for sunitinib, dacomitinib, palbociclib, bosutinib, and axitinib. Pharmacokinetic (PK) analyses were conducted based on Child-Pugh classification and NCIc. Review of 117 approved oncology compounds showed prevalent use of Child-Pugh classification for dedicated HI studies in noncancer subjects. NCIc is commonly used in cancer patient studies. NCIc tended to classify subjects as less impaired versus Child-Pugh (64.9%, 73.7%, a...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research