Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer

Abstract

Introduction This phase II trial investigated chemoradiation followed by surgery and 2years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60mg/m(2) (days 1 and 22), paclitaxel 60mg/m(2) (days 1, 8, 15, and 22), and 45Gy hyperfractionated radiotherapy for 3weeks followed by transhiatal esophagectomy. TM 20mg PO QD was started 4weeks post-op, and continued for 2years to maintain the ceruloplasmin level between 5 and 15mg/dl. Results Sixty-nine patients were enrolled (median age, 60years). Sixty-six patients underwent surgery and 61 patients had a complete resection. Histologic complete response rate was 10%. Twenty-one patients did not receive TM (metastases noted in the peri-operative period, prolonged post-operative recovery time, or patient refusal). Forty-eight patients started TM; 14 completed 24months of treatment, 11 completed 10-18months, 15 completed 2-8months, and 8 completed ≤1month. Twenty-seven patients had disease recurrence. With a median follow-up of 55months, 25 patients were alive without disease, 1 was alive with disease, and 43 have died. Three-year recurrence-free survival was 44% (95% CI, 32-55%) and the three-year overall survival was 45% (95% CI 33-56%). Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation.