title: 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 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60 mg/m(2) (days 1 and 22), paclitaxel 60 mg/m(2) (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.
authors: Division of Hematology/Oncology, Department of Internal Medicine, Weill Cornell Medical College, 1305 York Avenue, 7th floor, New York, NY 10021, USA. bjs2004@med.cornell.edu
authors: Bryan J
authors: BJ
authors: Schneider
authors: Julia Shin-Jung
authors: JS
authors: Lee
authors: James A
authors: JA
authors: Hayman
authors: Andrew C
authors: AC
authors: Chang
authors: Mark B
authors: MB
authors: Orringer
authors: Allan
authors: A
authors: Pickens
authors: Charlie C
authors: CC
authors: Pan
authors: Sofia D
authors: SD
authors: Merajver
authors: Susan G
authors: SG
authors: Urba
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008982:Molybdenum / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011182:Postoperative Care; D011300:Preoperative Care; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D008982:Molybdenum; C020809:tetrathiomolybdate; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil