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 New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

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: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>