Cox-2 Inhibition In Combination With Preoperative Chemoradiation For Ca Esophagus

e15607 Background: Squamous cell carcinoma of the thoracic esophagus (ESCC) is often diagnosed in advanced stage. Pre-operative chemoradiation is employed to downstage the disease before operation. Pathological complete response (pCR) was observed in around 20–40% of patients and was associated with improved survival. Cyclooxygenase 2 (COX-2) is overexpressed in ESCC and may contribute to chemo- and radio-resistance. This pilot study evaluates if COX-2 inhibition in combination with pre-operative chemoradiation will improve the response rate in ESCC. Methods: Patients with histologically confirmed ESCC undergo endoscopic ultrasound, ultrasound of neck and PET/ thoracic, abdominal CT for staging. Patients with disease which is considered potentially resectable are eligible. The primary and involved lymph nodes are irradiated to 40Gy in 20 fractions over 4 weeks with 2 cycles of concurrent cisplatin (100mg/sqm, D1, D22) and 5 fluorouracil (500mg/sqm, D1–5, D22–26). Celecoxib, a specific COX-2 inhibitor, 400mg bid, is started for 2 weeks before chemoradiation, continued throughout chemoradiation and for 4 more weeks after completion of chemoradiation. Patients are re-evaluated and esophagectomy is performed 6–8 weeks after completion of chemoradiation. Results: From 2004 to 2008, 32 patients were recruited. Pre-operative staging was stage II in 4, stage III in 25 and stage IVA in 3 patients. Celecoxib was well tolerated. 3 patients did not have full course of celecoxib: 1 complained of epigastric pain, 1 died early of disease, 1 had renal impairment after chemotherapy. 29 patients had esophagectomy performed after chemoradiation. Median follow-up after completion of chemoradiation was 11 months (range: 3 to 43 months). 23 patients (79.3%) had downstaging of the primary compared with pre-operative staging. The pCR rate in primary tumor was 51.7% (15/29 patients) and pCR rate in lymph nodes was 65.4% (17/26 patients). 3 years overall survival of patients who had esophagectomy was 79.3%. Conclusions: COX-2 inhibition in combination with pre-operative chemoradiation is well tolerated. Preliminary results of the pCR rates and survival are encouraging. Incorporation of COX-2 inhibition into multi-modality treatment of ESCC should be further investigated in a randomized trial. No significant financial relationships to disclose.