Investigational New Drugs

, Volume 31, Issue 2, pp 435–442 | Cite as

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

  • Bryan J. SchneiderEmail author
  • Julia Shin-Jung Lee
  • James A. Hayman
  • Andrew C. Chang
  • Mark B. Orringer
  • Allan Pickens
  • Charlie C. Pan
  • Sofia D. Merajver
  • Susan G. Urba


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.


Esophageal cancer Neoadjuvant chemoradiation Tetrathiomolybdate Cisplatin Paclitaxel 


Ethical standards

The trial was approved by the local Institutional Review Board and written informed consent was obtained from all patients.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Bryan J. Schneider
    • 1
    Email author
  • Julia Shin-Jung Lee
    • 2
    • 9
  • James A. Hayman
    • 3
  • Andrew C. Chang
    • 4
  • Mark B. Orringer
    • 4
  • Allan Pickens
    • 5
  • Charlie C. Pan
    • 6
  • Sofia D. Merajver
    • 7
    • 8
  • Susan G. Urba
    • 7
    • 10
  1. 1.Division of Hematology/Oncology, Department of Internal MedicineWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Biostatistics Core FacilityUniversity of Michigan Cancer CenterAnn ArborUSA
  3. 3.Department of Radiation OncologyUniversity of MichiganAnn ArborUSA
  4. 4.Department of Thoracic SurgeryUniversity of Michigan, A. Alfred Taubman Health Care CenterAnn ArborUSA
  5. 5.Department of Thoracic SurgeryEmory University Hospital,NE AtlantaUSA
  6. 6.Bellin Health Care SystemGreen BayUSA
  7. 7.Division of Hematology/Oncology, Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  8. 8.Department of Internal MedicineUniversity of Michigan Comp Cancer CtrAnn ArborUSA
  9. 9.Institute for Social Research Program in Survey MethodologyUniversity of MichiganAnn ArborUSA
  10. 10.Department of Internal MedicineUniversity of Michigan Comp Cancer CtrAnn ArborUSA

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