Weill CU study is first to show benefit of COX-2 drug for cancer treatment

By Timothy Paul

For the first time it has been shown that a drug called a COX-2 inhibitor might boost the effectiveness of chemotherapy in the treatment of cancer, according to a study by researchers at NewYork Weill Cornell Medical Center.

The study looks at non-small cell lung cancer (NSCLC), the most aggressive lung cancer and the leading cause of cancer death in the United States. This is the latest of Weill Cornell findings suggesting the benefits of COX-2 inhibitors for treatments of cancer and pre-cancerous conditions of the lung, colon, breast, esophagus, mouth and bladder.

The COX (cyclooxygenase) enzyme was first isolated in 1976, and in 1991 it was discovered that there are two enzymes, COX-1 and COX-2, the latter being the majority of the enzyme at the site of inflammation and the enzyme that catalyzes the synthesis of prostaglandins (PGs). Increased levels of COX-2 and PGs have been observed in a variety of malignancies including NSCLC.

The new study, published in the current issue of the Journal of Clinical Oncology, finds that patients with NSCLC treated with the drug celecoxib, a COX-2 inhibitor, administered in conjunction with the drugs paclitaxel and carboplatin, two common chemotherapeutic agents, results in lower levels of the PG molecule associated with tumor growth (prostaglandin E2, or PGE2), when compared with treatment with chemotherapy alone. Additionally, the treatment is shown to be feasible and safe.

"This study shows that celecoxib, by decreasing COX-2-derived PGE2, may be useful when given in combination with chemotherapy," said principal investigator Nasser Altorki, professor of cardiothoracic surgery at Weill Cornell and director of the division of thoracic surgery at NewYork Weill Cornell Medical Center. "Remarkably, for patients taking celecoxib, the amount of PGE2 present in the tumor was equivalent to amounts in a non-cancerous lung," he said.

A future trial led by Altorki will examine changes in tumor size and survival rates for NSCLC patients treated with chemotherapy alone vs. chemotherapy plus celecoxib.

The study, supported by a grant from Pharmacia Oncology and Pfizer, is co-authored by Andrew Dannenberg, co-director of NewYork-Presbyterian Hospital's Cancer Prevention Program and the Henry R. Erle-Roberts Family Professor of Medicine at Weill Cornell. Contributing authors from NewYork Weill Cornell Medical Center include David Yankelevitz, Kotha Subbaramaiah, Jeffrey Port, Roger Keresztes, Robert Korst, Douglas Flieder, Daniel Libby, Mark Pasmantier and Cathy Ferrara, R.N.