An early phase study pairing an experimental targeted therapy with a common anti-inflammatory produced promising results in patients with advanced lung cancer, researchers at UCLA's Jonsson Cancer Center reported.
Pairing the targeted therapy Tarceva with the anti-inflammatory drug Celebrex increased response rates in lung cancer patients by about three-fold, said Dr. Karen Reckamp, an assistant professor of hematology/oncology and lead author of the study. The research appears in the June 1 issue of Clinical Cancer Research, the peer-reviewed journal of the American Association of Cancer Research.
Previous laboratory studies at UCLA showed that a cell signaling pathway known as COX-2 may be linked to resistance to drugs like Tarceva, which block tumor cell growth by targeting the protein EGFR, or epidermal growth factor receptor. Researchers theorized that giving Tarceva with Celebrex, a COX-2 inhibitor, would help battle resistance and prove to be an affective combination against lung cancer.
Typically, about 10 percent of lung cancer patients respond to Tarceva. In Reckamp's study of the combination therapy, about 33 percent of patients responded.
"Tarceva alone is a great drug and has a lot of clinical benefits, but for a small proportion of patients," Reckamp said. "With this drug combination, we saw an increase in response rates, indicating we are overcoming some resistance. We also may be beginning to understand the mechanisms of that resistance."
Volunteers in the Phase I study, patients with advanced lung cancer that had failed to respond to all conventional therapies, took several Celebrex pills and one Tarceva pill each day. After eight weeks, researchers looked at response rates. Patients were able to stay on the study as long as they didn't experience tumor growth. The longest duration of response was 93 weeks, Reckamp said, about three to four times longer than the average duration of response for a patient with advanced lung cancer.
The study was part of the Specialized Program of Research Excellence (SPORE) in lung cancer at UCLA's Jonsson Cancer, a program funded by the National Cancer Institute at top research institutions nationwide to find better and more effective ways to prevent, detect and treat lung cancer.
"This trial is an important early step in utilizing combination targeted therapies in lung cancer," said Dr. Steven Dubinett, director of UCLA's lung cancer SPORE and a professor of pulmonary and critical care medicine. "Dr. Reckamp's trial is the first to study increasing doses of a COX-2 inhibitor in lung cancer in an attempt to define an optimal biological dose. Larger trials of combination therapies utilizing this dose will now be required."