CHICAGO—Gene-expression profiling, combined with a novel chemoradiation regimen, may predict pathologic complete response in patients with esophageal cancer, according to new data presented at the 46th annual meeting in specific cancer populations. of the American Society of Clinical Oncology. New studies presented at this meeting highlighted several new “genetic fingerprinting” techniques that may improve and guide chemo therapy.
Researchers looked at pathologic complete response rate and toxicity in a phase 2 trial involving 36 patients with stage II to IVa esophageal cancer, 29 (81%) of whom had undergone surgery in the course of their treatment. The treatment consisted of three 85-mg/m2 doses of oxaliplatin over the course of a month, a 625-mg/m2 twice-daily dose of oral capecitabine, and radiation therapy, followed by surgery 4 to 6 weeks later. Two cycles of oxaliplatin and capecitabine were given postoperatively. Gene-expression profiling (using microarrays by Agilent Technology) was conducted on primary tumor tissue.
The researchers have found that eight of the 29 patients who had their esophagus removed following the oxaliplatin regimen had no cancer in the surgical specimen (a 28% pathologic complete response rate). “Another clear result is that this regimen is very welltolerated by patients without significant side effects,” said study investigator Nikhil Khushalani, MD, who is an assistant professor of medicine at Roswell Park Cancer Institute. “There appear to be several gene pathways that are enriched when studying different subgroups, the pathologic complete re sponse group versus the nonpathologic complete response group.”
The study continues to accrue patients, and Khushalani expects to have mature survival data by fall 2010. “I believe this is an efficacious regimen, and it’s definitely well-tolerated,” he said. “We hope that the exploratory geneexpression profiling results will translate into clinically meaningful hypotheses that can be validated in a large, preferably multicenter study.”
Genetic profiling to identify trastuzumab resistance in breast cancer patients Other researchers at Roswell Park Cancer Institute are hoping to determine whether genetic profiling may effectively identify which breast cancer patients are most likely to respond to the drug trastuzumab.
Trastuzumab interferes with a protein, known as the human epidermal growth factor receptor type 2 (HER2), which is linked to breast cancer. However, a high number of breast cancer patients (approximately 50%) don’t respond to the drug and experience recurrence. Currently, there is great interest in research that might elicit factors that drive responses.
Over the past 2 years, researchers looked at 41 breast carcinoma cases in which amplified HER2 levels were seen and for which fresh frozen tissue was available. Of these patients, 12 were treated with trastuzumab and three (25%) experienced recurrence. Among the 11 patients not treated with the drug, microarrays were used to identify differentially expressed genes for trastuzumab (responsive vs resistant).
The investigators found that the differentially expressed genes for recurrence or nonrecurrence were distinct between the group treated with tras tuzumab and the group that was not treated with the drug. The researchers hope that differential expression of key genes identified in this study may offer insights into trastuzumab resistance among breast cancer patients. It is hoped that this type of technology fingerprinting can lead to new potential biomarkers for diagnosis, prognosis, and treatment.
“The group that was treated with trastuzumab and developed recurrence had a genetic makeup different from those who were not treated and developed recurrence,” said study investigator Thaer Khoury, MD, who is an assistant professor of pathology and laboratory medicine at Roswell Park Cancer Institute. “The idea from the beginning was to know why these patients who are treated with tras - tuzumab develop recurrence and why the others did not. There is definitely something going on, and we’re starting to understand these mechanisms.”
Khoury, who presented the study findings at the meeting, said they should be of particular interest to clinicians working in this area of cancer. The message about treatment and how it should be guided is now changing, as molecular markers are complementing clinical markers
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