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

Investigational New Drugs - Tập 31 - Trang 435-442 - 2012
Bryan J. Schneider1, Julia Shin-Jung Lee2,3, James A. Hayman4, Andrew C. Chang5, Mark B. Orringer5, Allan Pickens6, Charlie C. Pan7, Sofia D. Merajver8,9, Susan G. Urba8,9
1Division of Hematology/Oncology, Department of Internal Medicine, Weill Cornell Medical College, New York, USA
2Biostatistics Core Facility, University of Michigan Cancer Center, Ann Arbor, USA
3Institute for Social Research Program in Survey Methodology, University of Michigan, Ann Arbor, USA
4Department of Radiation Oncology, University of Michigan, Ann Arbor, USA
5Department of Thoracic Surgery, University of Michigan, A. Alfred Taubman Health Care Center, Ann Arbor, USA
6Department of Thoracic Surgery, Emory University Hospital,, NE Atlanta, USA
7Bellin Health Care System, Green Bay, USA
8Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA
9Department of Internal Medicine, University of Michigan Comp Cancer Ctr, Ann Arbor, USA

Tóm tắt

Introduction This phase II trial investigated chemoradiation followed by surgery and 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60 mg/m2 (days 1 and 22), paclitaxel 60 mg/m2 (days 1, 8, 15, and 22), and 45 Gy hyperfractionated radiotherapy for 3 weeks followed by transhiatal esophagectomy. TM 20 mg PO QD was started 4 weeks post-op, and continued for 2 years to maintain the ceruloplasmin level between 5 and 15 mg/dl. Results Sixty-nine patients were enrolled (median age, 60 years). 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 24 months of treatment, 11 completed 10–18 months, 15 completed 2–8 months, and 8 completed ≤1 month. Twenty-seven patients had disease recurrence. With a median follow-up of 55 months, 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.

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