Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lung cancer patients in Japan, United States react differently to the same chemotherapy regimen

07.06.2004


Survival, toxicity greater in Japanese patients, “common arm” analysis shows



A chemotherapy regimen commonly used to treat non-small cell lung cancer is both more effective and more toxic in Japanese patients than in American patients, researchers reported Saturday at the annual meeting of the American Society of Clinical Oncologists. The first of its kind, this analysis underscores the importance of genetic variations in medicine and points to a need for increased international collaboration in trials of new cancer treatments.

"Results of a cancer clinical trial performed in one part of the world may not necessarily hold true for populations in other regions," said lead investigator David Gandara, director of clinical research at UC Davis Cancer Center and professor of medicine at the UC Davis School of Medicine. "We need to be cautious when we extrapolate from one population to another."


The analysis compared results from two phase III clinical trials designed to evaluate the relative effectiveness of various treatments for patients with advanced non-small cell lung cancer. One trial was conducted in the United States, the other in Japan. The two trials were carefully structured from the outset, through a lengthy series of meetings between U.S. and Japanese investigators and representatives of the Japanese Ministry of Health, to have a "common arm." The approach allowed researchers to make direct comparisons of one chemotherapy regimen -- paclitaxel and carboplatin -- in both populations. Patients in both trials were closely matched in terms of age, gender, disease stage and tumor type.

The collaboration is the first to prospectively design a "common arm" in a U.S. cooperative group trial and in one conducted in another country. Median survival time was 12 months for the Japanese patients in the paclitaxel-carboplatin arm of the study, versus nine months for U.S. patients receiving the same regimen. Half of the Japanese patients (51 percent) survived one year, versus only slightly more than a third (37 percent) of the American patients.

"The reasons for the increased survival among the Japanese patients remain to be determined, but the implications of this observation are of considerable interest," Gandara said.

The longer survival in the Japanese group was especially striking because those patients had to be given a lower dose of paclitaxel due to toxicity. Even with the lower dose, the Japanese patients were able to complete fewer cycles of the chemotherapy regimen, and some side effects were more severe.

The U.S. patients received 225-milligram doses of paclitaxel; the Japanese patients received 200-milligram doses. Earlier phase I studies of paclitaxel in the U.S. and Japan set these as the maximum tolerated doses for each population.

Despite the reduced dose, only one in four of the Japanese patients (24 percent) completed three cycles of the paclitaxel-carboplatin regimen, versus 100 percent of the U.S. patients. And only about one in 10 Japanese patients (11 percent) completed six cycles, versus more than a third of the U.S. patients (36.5 percent).

Neutropenia, in which levels of infection-fighting white blood cells drop to dangerous levels, was more than twice as common in the Japanese patients. Neutropenia accompanied by fever was more than five times as common in the Japanese patients.

On the other hand, one side effect, neuropathy, was more common in the U.S. patients, for good reason, according to Gandara. Neuropathy results from cumulative exposure to many cycles of paclitaxel, and the U.S. patients completed more cycles. Neuropathy is characterized by tingling, numbness or pain due to nerve damage.

Patients in both trials received equivalent levels of carboplatin.

Gandara and his colleagues believe the differences between the U.S. and Japanese patients are likely due to genetic differences in drug metabolism, an area of science known as pharmacogenomics. Recent research has identified specific genes involved in paclitaxel metabolism, and these genes may prove different from one ethnic group to another.

"These findings underscore both the importance of global clinical trials, and the importance of ensuring that we do them carefully. It will be critical to take into account possible pharmacogenomic differences among populations as we move toward global trials," Gandara said.

The U.S. trial was conducted through the Southwest Oncology Group, one of the country’s largest National Cancer Institute-sponsored cancer clinical trials cooperative groups, comprising 283 institutions in the United States and Canada. The Japanese study was conducted through the FACS group, or Four-Arm Comparative Study Group.

The combination of paclitaxel and carboplatin is commonly used to treat non-small cell lung cancer in the U.S., but had never been studied in a large clinical trial in Japan.

While major pharmaceutical companies have conducted global trials of investigational drugs, there is no mechanism at present to conduct joint NCI-sponsored trials internationally. "We hope this analysis will serve as a model for future prospective comparisons of cooperative group trials," Gandara said.

Gandara is a member of the ASCO board of directors, and serves as its secretary/treasurer. A prominent lung cancer specialist, he also chairs the SWOG Lung Committee. Under his leadership, UC Davis Cancer Center for the past two years has ranked first among the 283 SWOG sites in the number of patients enrolled in clinical trials.

UC Davis Cancer Center is the only National Cancer Institute-designated cancer center between San Francisco and Portland, Ore., a region the size of Pennsylvania. Its Integrated Cancer Research Program with Lawrence Livermore National Laboratory is the nation’s first such partnership between a major cancer research center and a national laboratory.


Additional Contact information for Claudia Morain can be reached at 530-219-5053 through June 6, 2004 and 916-734-9023 beginning June 7, 2004

Claudia Morian | EurekAlert!
Further information:
http://www.ucdmc.ucdavis.edu/medical_center/index

More articles from Studies and Analyses:

nachricht The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>