Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results.

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.