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| |  ASCO: Different Ethnicities React Differently to Same Chemotherapy Regimen By Charlene Laino NEW ORLEANS, LA -- June 6, 2004 -- Results of clinical trials conducted in 1 country cannot always be extrapolated to residents of other countries, according to a comparison of phase 3 trials involving patients with non-small-cell lung cancer conducted in Japan and the United States. The study, presented here on June 5th at the American Society of Clinical Oncology 40th Annual Meeting, showed that a combination of paclitaxel and carboplatin is more effective, but carries greater toxicity, in Japanese patients than in American patients with similar characteristics at baseline. "Results of a cancer clinical trial performed in 1 part of the world may not necessarily hold true for populations in other regions," said lead investigator David Gandara, MD, director of clinical research, University of California Davis Cancer Center and professor of medicine, University of California Davis School of Medicine, Sacramento, California. "We need to be cautious when we extrapolate from one population to another." The study, the first of its kind, underscores the importance of genetic variations within populations and points to a need for increased international collaboration in clinical trials, he said. For the study, the researchers designed and conducted 2 prospective separate phase 3 trials testing a regimen of paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. The studies had identical eligibility requirements, with patients in both the Japanese and American trials closely matched in terms of age, gender, disease stage, and tumor type. Patients in both trials were a mean age of 63 years and about one third of patients were women. Eighty-one percent of patients in the Japanese Four Arm Cooperative Study (FACS) had stage IV disease, compared with 87% in the US trial, a nonsignificant difference. The treatment regimen was also similar although patients in the Japanese study received 100 mg/m2 of paclitaxel, while those in the US Southwest Oncology Group Trial received 225 mg/m2 of paclitaxel. The area under the curve for carboplatin was 6 in both studies. The results showed that median survival time was 12 months for the Japanese patients in the paclitaxel-carboplatin arm of the study, compared with 9 months for US patients receiving the same regimen, Dr. Gandara reported. One-year survival rates were 51% in the Japanese trial versus 37% in the American study, he said. Despite the reduced dose of paclitaxel, 24% of the Japanese patients completed 3 cycles of the paclitaxel-carboplatin regimen, Dr. Gandara said, compared with 100% of the US patients. And about 1 in 10 Japanese patients completed 6 cycles versus more than one third of the US patients. Japanese patients were twice as likely to develop neutropenia and 5 times more likely to develop febrile neutropenia than American patients, Dr. Gandara said. But neuropathy, a known side effect of cumulative exposure to paclitaxel, was more common in US patients, he said. Dr. Gandara hypothesized that the differences in response to the drugs were likely due to pharmacogenomics. "UGT1A1 polymorphism is lower in Japan and higher [in the US]," he said. "So Japanese patients have slower metabolism of paclitaxel. They get more bang for the buck." "Clinicians need to be careful when adopting therapies that were tested in other parts of the world," Dr. Gandara said in an interview. There are other examples of differences in responses among different ethnicities, he added. "For example, when irinotecan (CPT-11) was tested for colorectal cancer in Japan, it proved very effective with few side effects," he said. "In the United States it was also effective but there were many more side effects and patients' response to the drug was unpredictable."
[Presentation title: Japan-SWOG Common Arm Analysis of Paclitaxel/Carboplatin in Advanced Stage Non-Small Cell Lung Cancer (NSCLC): A Model for Prospective Comparison of Cooperative Group Trials. Abstract 7007]
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