LOS ANGELES ? Celebrex (celecoxib), the Cox-2 inhibitor, and Tarceva (erlotinib), the EGFR-receptor inhibitor, have been teamed with some preliminary success to inhibit late-stage non-small-cell lung cancer.
LOS ANGELES, June 1 ? Celebrex (celecoxib), the Cox-2 inhibitor, and Tarceva (erlotinib), the epidermal growth factor-receptor (EGFR) inhibitor, have been teamed with some preliminary success to inhibit late-stage non-small-cell lung cancer.
Over-expression of Cox-2 in tumor cells was seen in preclinical studies to cause resistance to drugs like Tarceva, which block tumor cell growth by targeting the EGFR, according to Karen Reckamp, M.D., of the University of California at Los Angeles.
Dr. Reckamp and colleagues hypothesized that combining Celebrex with Tarceva would improve response rates; and they initiated a Phase I study to find the optimal biological dose and establish the toxicity profile of the combination.
As a secondary endpoint, the researchers included clinical response to the drug pairing.
Typically, Dr. Reckamp said, about one patient in 10 responds to Tarceva alone. Yet with the combination, 33% had a partial clinical response, and an additional 24% achieved stable disease.
"Tarceva alone is a great drug and has a lot of clinical benefits, but for a small proportion of patients," Dr. Reckamp said. "With this drug combination, we saw an increase in response rates, indicating we are overcoming some resistance."
In the June 1 issue of Clinical Cancer Research, Dr. Reckamp and colleagues presented safety data on 21 participants with stage IIIB and/or IV non-small-cell lung cancer, who received increasing doses of Celebrex, from 200 mg to 800 mg twice daily, as well as 150 mg/day of Tarceva.
The most common toxicities were rash and skin-related effects, reported by 86% of patients, but there were no dose-limiting toxicities and no cardiovascular toxicities related to the study drugs, the researcher found.
One patient?in the group taking 200 mg twice daily of Celebrex?suffered a myocardial infarction, but the event was after he stopped taking the drug and thought to be unrelated, because he had a previous history of MI. He had been enrolled before the spate of warnings about cardiovascular risks of Celebrex.
The optimal dose of Celebrex, measured by decrease in urinary prostaglandin E-M, was 600 mg twice a day.
The researchers also reported response data for 21 of the patients; the other patient had his Celebrex interrupted following the FDA warning regarding cardiovascular safety.
The researchers evaluated response rates after eight weeks, but patients stayed on the study until tumor progression. The longest duration of response was 95 weeks, Dr. Reckamp said, which is more than three times longer than the average duration of response for a patient with advanced lung cancer.
The researchers are planning a Phase II study, expected to start later this year, to confirm the efficacy of the combination therapy and to try to increase their understanding of Tarceva resistance, Dr. Reckamp said.