Preoperative chemoradiation and postoperative adjuvant tetrathiomolybdate for patients with resectable esophageal cancer

Abstract

e15504 Background: Tetrathiomolybdate (TM) is an oral copper chelator. Copper is necessary for blood vessel growth, and so TM functions as an antiangiogenic agent. Methods: Pts with resectable esophageal cancer were treated at the University of Michigan with chemoradiation followed by surgery, and then 2 years of TM. Chemoradiation was cisplatin 60 mg/m2 on days #1 and 22, paclitaxel 60 mg/m2 on days #1, 8, 15, and 22, and radiation 1.5 Gy fractions b.i.d. x 3 weeks to a total of 45 Gy. Transhiatal esophagectomy was performed on approximately day #50. TM 20 mg p.o. q.d. was started approximately 4 weeks post-op, and continued for 2 years. Doses were adjusted to maintain the ceruloplasmin level between 5 and 15. Results: Between 1/23/02 and 1/24/06, 69 pts were enrolled. Pt characteristics: males - 62 (90%), females - 7 (10%); median age - 60 (range 42–74); adenocarcinoma - 56 (81%), squamous cell carcinoma 13 (19%). The chemoradiation was well tolerated: grade 3 leukopenia in 15 pts (22%), and 17 pts (25%) required feeding tubes. 66 pts went to surgery. 61 pts had a complete resection; 4 pts had metastases discovered at surgery, and 1 pt had extensive positive margins. Histologic complete response rate was 10%. 21 pts never received TM because of metastases noted in the peri-operative period, long post-op recovery time, or pt refusal. 48 pts started TM after surgery and it was well tolerated. Grade 3 toxicities were diarrhea -2 (3%), nausea - 2 (3%), dizziness - 2 (3%). 13 pts completed the full 24 mos of treatment, 12 completed 10–23 mos, 15 completed 2–8 mos, and 8 completed only 1 month or less. 27 pts have had disease recurrence, the majority (23 of the 27) of which was distant. Current status of pts with median follow-up time of 55 months: 25 alive and disease-free, 1 alive with disease, and 43 have died. 3-year survival probability is 47% (95% CI 35%-58.6%). 3-year recurrence-free probability is 51% (95% CI 38%- 62.7%). Conclusions: TM is an antiangiogenic agent which is fairly well tolerated. Prolonged adjuvant treatment over 2 years is difficult but not impossible to complete. Disease-free survival and overall survival are promising when compared to historical controls treated with a very similar chemoradiation regimen without TM in the past at the University of Michigan. [Table: see text]