A City of Hope researcher has identified biomarkers that may help predict which nonsmall cell lung cancer patients will benefit most from an investigational combination therapy. The findings represent a movement toward more personalized treatments for the disease.
Karen L. Reckamp, M.D., assistant professor in the divisions of Medical Oncology & Therapeutics Research and Hematology & Hematopoietic Cell Transplantation, presented data from her study on the combination therapy at the 2007 American Society of Clinical Oncology Annual Meeting in June.
Reckamp began by studying the use of celecoxib (Celebrex), a COX-2 inhibitor, and erlotinib (Tarceva), a drug that targets epidermal growth factor receptor (EGFR), in a phase I trial for nonsmall cell lung cancer. When activated, EGFR signals cells to divide and grow. Many cancers overexpress EGFR, which contributes to uncontrolled cell division and tumor development.
In addition to EGFR, most nonsmall cell lung tumors also overexpress COX-2, which may interfere with erlotinib’s effectiveness. Using celecoxib to inhibit COX-2, though, may help.
Results from the trial pairing celecoxib with erlotinib were promising, leading Reckamp and colleagues to dig further. Her study, presented at the recent meeting, identified two proteins linked to how well patients responded to the combination therapy. These proteins may potentially serve as biomarkers that physicians can use to tailor a personalized anticancer therapy for patients with nonsmall cell lung cancer, she said.
These two proteins are called serum soluble E-cadherin (sEC) and matrix metalloproteinase (MMP)-9.
“We found a significant decrease in sEC levels in patients who demonstrated significant tumor shrinkage with treatment in comparison to patients who had only stable tumor size or an increase in tumor size,” said Reckamp, a member of the Lung Cancer and Thoracic Oncology Program. “Patients who showed the best tumor response to treatment had significantly lower MMP-9 levels taken prior to treatment than patients who did not have a significant decrease in tumor size with combination therapy.”
Reckamp plans to conduct a randomized phase II trial comparing the combination of celecoxib and erlotinib against erlotinib and a placebo among patients with an advanced form of the cancer. She expects to continue assessing biomarkers in that trial.
Lung cancer takes more lives in the United States than any other cancer, causing about 160,000 deaths each year. According to the American Cancer Society, more than 213,000 people will be diagnosed with lung cancer this year. Nonsmall cell is the most common form of the disease, comprising about 80 percent of lung cancer cases in the U.S.