Related Experiment Video

Updated: Mar 8, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.5K

Risks and benefits of phase I liver dysfunction studies: should patients with severe liver dysfunction be included in

Christos Fountzilas1,2, Selena Stuart1,3, Brian Hernandez1

  • 1University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA.

Investigational New Drugs
|January 20, 2017
PubMed

Insights

Cancer patients in phase I trials with liver dysfunction have poor survival. Albumin levels and liver function classification are key factors for selecting patients for these studies.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Translational Medicine

Background:

  • Phase I trials aim to assess novel agents' safety and pharmacokinetics in cancer patients with organ dysfunction.
  • The clinical benefit of these trials for patients with liver or kidney dysfunction is not well established.

Purpose of the Study:

  • To evaluate the survival outcomes and identify prognostic factors in cancer patients with liver dysfunction participating in Phase I trials.

Main Methods:

  • A retrospective review of 170 patients across 15 liver dysfunction studies was conducted.
  • Patients were grouped based on the National Cancer Institute-Organ Dysfunction Working Group criteria or Child-Pugh Score.

Main Results:

  • The median survival for the entire cohort was two months, significantly lower (one month) for patients with severe liver dysfunction.
  • Univariate analysis indicated improved survival for patients with normal/mild liver dysfunction, no liver tumor, good performance status, higher serum albumin, and lower bilirubin, AST, and ALP.
  • Multivariate analysis confirmed serum albumin and liver function classification as significant prognostic factors for survival.

Conclusions:

  • Cancer patients with liver dysfunction in Phase I trials exhibit poor survival rates.
  • Current criteria for patient selection may need refinement, with serum albumin levels showing promise as a more optimal selection criterion.
Keywords:
Liver dysfunctionPhase I studyPrognostic modelSurvival

More Related Videos

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases05:56

Evaluation of the Feasibility, Safety, and Accuracy of an Intraoperative High-intensity Focused Ultrasound Device for Treating Liver Metastases

Published on: January 9, 2019

8.3K
Author Spotlight: Advancing Liver Regeneration Research through ALPPS Mouse Model06:45

Author Spotlight: Advancing Liver Regeneration Research through ALPPS Mouse Model

Published on: January 19, 2024

1.4K

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
245
Phase I Oxidative Reactions: Overview01:19

Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
920
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
305
Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
5.4K
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
841
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation01:22

Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
1.1K