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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>