Treatment > Nonsteroidal Anti-Inflammatory Drugs

Meeting Abstract

Celecoxib (Celebrex), a selective COX-2 inhibitor, enhances the response to preoperative paclitaxel/carboplatin in early stage non-small cell lung cancer

Nasser K Altorki, Roger S Keresztes, Jeffrey L Port, Douglas B Flieder, Cathy A Ferrara, Mark W Pasmantier, Daniel M Libby, David Yankelevitz, Andrew J Dannenberg

Weill Medical College of Cornell University, New York, NY

Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of human tumors including non-small cell lung cancer (NSCLC). 
Overexpression of COX-2 derived prostaglandins may contribute to carcinogenesis by reducing immune surveillance, inhibiting apoptosis and/or stimulating angiogenesis. 
In this study, we assessed the role of the COX-2 inhibitor celecoxib as an adjunct to preoperative chemotherapy in patients with resectable NSCLC. 

Methods. Twenty-three patients were entered into a phase II trial of preoperative chemotherapy and celecoxib for stage IB - IIIA NSCLC. 
Two cycles of paclitaxel (225 mg/m2) and carboplatin (AUC 6) were given three weeks apart. 
Celecoxib was given orally at 400mg BID from day 1 until the day of surgery. 
Surgery was performed on days 42-56. 

Results. Twenty-three patients were enrolled: 16 men and 7 women. 
Median age was 64. 
Preoperative stages were IB=13, IIB=3, IIIA=7. 
Thus far, 16 completed the prescribed treatment plan including surgical resection. 
There was no unexpected chemotherapy-related toxicity. 
Twelve of 16 had a major clinical response (8 partial; 4 complete) and 4 had stable disease. 
All 16 underwent resection (11 lobectomies, 2 bilobectomies and 3 pneumonectomies). 
On histological examination, a clinically important pathological response was seen in six patients (37%), with all having a greater than 95% tumor necrosis. 
There was one postoperative death. 

Conclusions. In comparison to historical response rates of induction paclitaxel/carboplatin for early stage NSCLC (clinical response 56%, pathological response 6%), these data suggest that COX-2 inhibition may significantly enhance the response to preoperative chemotherapy. 
Confirmatory trials are planned.

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