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

21.06.2007
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:
http://www.stjude.org

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>