In an effort to determine why, David Gandara, director of clinical research at the University of California, Davis, launched a clinical trial that closely matched American and Japanese patients by gender, age and severity of illness.
The discrepancy lies in the genes, Gandara announced today during a press conference at the annual meeting of the American Society of Clinical Oncology in Chicago. "When we looked at the patient outcomes, [we found that] it wasn't race that dictated the outcome, it was the genotype," he told Scientific American Online. Gandara, who also heads up lung cancer trials at the Southwest Oncology Group in Sacramento, one of the largest federally funded cancer trials network in the U.S., acknowledged, however, that more study is needed, given the small number of patients (156) involved.
All of the volunteers received the same "classic combination" of chemotherapy agents: carboplatin, a platinum-based drug that damages the DNA of tumor cells, and paclitaxel (sold under the name Taxol), which disrupts tumor cell division, marking them for programmed cell death. After one year, more than 50 percent of the Japanese patients were still alive, compared with only 37 percent of the Americans, who were mostly white. The Japanese subjects, however, were almost three times more likely to experience side-effects, the most prominent being neutropenia, a low count of disease-fighting white blood cells.
"In this study we were able to get the host DNA," Gandara says, noting that when researchers analyzed blood samples from patients, there were four key genes found to vary between the patients who lived and the ones who died. "These genes are responsible for the metabolism of Taxol or how cells repair damage from platinum compounds."
In patients with a particular variation of one of these genes (called CYP3A4), lung cancer took 2.75 times as long to progress as it did in subjects with a different version of it. This advantageous gene variant was more common in the homogeneous Japanese population than in the multiethnic American group.
The study, according to Gandara, indicates that "the DNA of a host is [just as] important as the tumor DNA" in determining which course of treatment will be most successful. He notes that a standard part of care in breast cancer cases is a test to determine the activity of the Her2 gene in the patient. If levels are found to be high, doctors often use a therapy that includes the drug Herceptin, because it is known to inhibit Her2's activity, which has been found to encourage cancer progression. "When something becomes important enough," Gandara says, "it gets translated into the standard of care." And he predicts that genetic testing may one day become standard in treating lung cancer patients.