Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


St. Jude shows gene test not needed if cancer drug given in low doses

Researchers show that delaying treatment with irinotecan to test for gene linked to drug side effects is not necessary when the drug is given in low doses for 2 weeks

Investigators at St. Jude Children's Research Hospital have shown that when the cancer drug irinotecan is given in low doses for multiple days, it eliminates the need to delay treatment to perform costly genetic testing that determines if the patient is at risk for serious treatment side effects, such as neutropenia. Neutropenia is an abnormal reduction in the numbers of immune cells, called neutrophils; the disorder leaves individuals more vulnerable to infections.

The finding means that clinicians can begin treatment sooner and eliminate the cost of this specialized test, which determines if the child carries a variation in the gene UGT1A1 that is linked to this side effect of neutropenia. By giving the drug in small doses for two weeks instead of the standard single large dose once a month, children can begin treatment with irinotecan immediately. Irinotecan is used to treat childhood solid tumors such as neuroblastoma, sarcomas and kidney tumors.

A report on this study is in the June 20 issue of the “Journal of Clinical Oncology.”

UGT1A1 makes an enzyme that modifies the activated form of irinotecan, a molecule called SN-38, so the body can easily remove it. Variations of this enzyme, especially one called UGT1A1*28, do not work as well and allow SN-38 to remain in the body at high levels for an extended period of time, causing side effects.

Like many genes, UGT1A1 has a series of DNA building blocks called thymidine and adenine (TA) repeating several times just in front of the gene itself. This area, called the promoter region, acts as an “on” switch that triggers the reading of the gene. The normal UGT1A1 has six copies of TA in front of it, while UGT1A1*28 has seven.

Previous studies had shown that when adults who carry two copies of the UGT1A1*28 gene variation received a single high dose of irinotecan, they suffered severe diarrhea or neutropenia, said Clinton Stewart, Pharm.D., associate member of the St. Jude Department of Pharmaceutical Sciences and the report’s first author.

“The U.S. Food and Drug Administration requires the irinotecan package labeling to indicate that patients with UGT1A1*28 are at increased risk for neutropenia and that clinicians should consider using a reduced dosage for these individuals,” Stewart said. “Based on this warning, we wanted to determine if children with the UGT1A1*28 gene variation were likely to suffer the same toxicity even if they received irinotecan in 10 small doses over two weeks instead of one large dose.”

The St. Jude team conducted a retrospective study of 74 children who had received this low-dose treatment for any of a variety of solid tumors. A total of 27 children had both copies of the normal gene UGT1A1 with six copies of TA in the promoter region; 36 had one normal and one UGT1A1*28 gene with seven copies of TA; and nine had two copies of UGT1A1*28.

The researchers found no association between UGT1A1*28 and either diarrhea or neutropenia—even if the patient had two copies of this gene when irinotecan was given at the reduced dose. Therefore, the researchers concluded that it was not useful to test patients to determine if they had UGT1A1*28.

“This is a negative finding in the sense that the UGT1A1*28 variation does not seem to predict toxic responses in patients treated with low-dose irinotecan,” said Lisa McGregor, M.D., Ph.D., assistant member of the St. Jude Department of Oncology and the report’s senior author. “But it should help clinicians design effective and safe irinotecan treatments for individual children.”

Summer Freeman | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>