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Chemotherapy Induces the Expression of Cyclooxygenase-2 in Non–Small Cell Lung Cancer

Authors' Affiliations: ¹ Department of Cardiothoracic Surgery and ² Medicine, Weill Medical College of Cornell University; and ³ Urology and ⁴ Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Andrew J. Dannenberg, Department of Medicine, Weill Medical College of Cornell University, Room F-206, 525 East 68th Street, New York, NY 10021. Phone: 212-746-4403; Fax: 212-746-4885; E-mail: ajdannen{at}med.cornell.edu.

Purpose: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E₂ (PGE₂) in patients with non–small cell lung cancer (NSCLC).

Experimental Design: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE₂ in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17).

Results: Levels of intratumoral PGE₂ were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE₂ were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98).

Conclusions: Treatment with chemotherapy led to increased amounts of COX-2 and PGE₂ in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE₂ but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy.

Key Words: cyclooxygenase-2 • prostaglandins • neoadjuvant chemotherapy

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