Related Experiment Video

Updated: May 14, 2026

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
13:19

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

A phase II study of sunitinib in advanced hepatocellular carcinoma

Carlo Barone1, Michele Basso, Marco Biolato

  • 1Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. carlobarone@rm.unicatt.it

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|February 16, 2013
PubMed
Abstract

Insights

Sunitinib showed limited efficacy and significant toxicity in advanced hepatocellular carcinoma patients. High rates of severe adverse events and early deaths were observed, questioning its use.

Area of Science:

  • Hepatocellular Carcinoma Research
  • Oncology Drug Efficacy
  • Clinical Trial Analysis

Background:

  • Sorafenib was the first drug to improve survival in advanced hepatocellular carcinoma (HCC) patients in 2007.
  • The study aimed to evaluate sunitinib, a targeted therapy, in HCC treatment.

Purpose of the Study:

  • To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma.
  • To determine the tolerability and response rates of sunitinib in this patient population.

Main Methods:

  • A single-arm, open-label, phase II clinical trial was conducted.
  • Eligibility criteria included advanced HCC, no prior chemotherapy, and Child-Pugh score ≤B8.
  • Patients received sunitinib 50mg daily on a 4-weeks-on, 2-weeks-off schedule.

Main Results:

  • 34 patients with advanced HCC were enrolled between 10/2007 and 10/2010.
  • Sunitinib led to a significant worsening of liver function and high rates of grade 3/4 adverse events (80%), including fatigue, liver failure, and encephalopathy.
  • Median overall survival was 5.8 months, with 18% of patients dying within 60 days; partial response was seen in 12%.

Conclusions:

  • The 50mg/d dose of sunitinib is associated with a high incidence of severe adverse events in advanced HCC.
  • Toxicity remains a significant concern even at a reduced dose of 37.5mg/d.
  • While sunitinib demonstrated potential for prolonged response in a subset of patients, its overall safety profile is problematic for HCC treatment.
Keywords:
Alpha-fetoproteinAminopyrineMethacetinPET

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

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-308:36

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Published on: April 7, 2023

Related Concept Videos

Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Phase II Reactions: Miscellaneous Conjugation Reactions01:19

Phase II Reactions: Miscellaneous Conjugation Reactions

Phase II biotransformations are detoxification mechanisms that conjugate xenobiotics with endogenous substances, neutralizing their toxicity.
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...