Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer

• Main Authors: Cleary, James M., Mamon, Harvey J., Szymonifka, Jackie, Bueno, Raphael, Choi, Noah, Donahue, Dean M., Fidias, Panos M., Gaissert, Henning A., Jaklitsch, Michael T., Kulke, Matthew H., Lynch, Thomas P., Mentzer, Steven J., Meyerhardt, Jeffrey A., Swanson, Richard S., Wain, John, Fuchs, Charles S., Enzinger, Peter C.
• Other Authors: Univ Arizona, Ctr Canc, St Josephs Hosp & Med Ctr
• Language: en
• Published: BioMed Central 2016
• Subjects: Esophageal cancer; Neoadjuvant therapy; Chemoradiation; Cyclooxygenase 2 inhibition
• Online Access: http://hdl.handle.net/10150/618723; http://arizona.openrepository.com/arizona/handle/10150/618723

Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. Methods: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Results: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. Conclusions: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.