E2205: A phase II study to measure response rate and toxicity of neoadjuvant chemoradiotherapy (CRT) with oxaliplatin (OX) and infusional 5-fluorouracil (5-FU) plus cetuximab (C) followed by postoperative docetaxel (DT) and C in patients with operable adenocarcinoma of the esophagus.

Abstract

4064 Background: One approach to treating resectable esophageal adenocarcinoma is CRT followed by surgery; however, recurrence is common. To improve on this, we designed a single-arm, phase II trial that added an EGF-R inhibitor, C, to CRT. Methods: We aimed to increase the pathologic complete response (pCR) rate from 25% to 45%. A Simon two-stage design (α and β of 0.10) required pCR/enrolled of 5/18 for stage I and 14/40 total. 22 pts enrolled. CRT: OX 85 mg/m2 D1, 15, 29; infusional 5-FU 180 mg/m2/24 hr × 35 days; C 400 mg/m2 D1 then 250 mg/m2 D8, 15, 22, 29 and radiation (IMRT allowed) 180 cGy/day × 25 fractions (M-F). Following esophagectomy, adjuvant chemotherapy (CT): weekly DT 35 mg/m2 and C 250 mg/m2 5/6 weeks × 2 cycles. Endpoints: efficacy by pCR rate and toxicity. Results: Of 22 patients enrolled, 18 had surgery (C reaction off study, died PE 4 days after CRT, G3 diarrhea during CRT died disease progression, died sepsis/hypoxia during CRT). pCR = 7 patients. 13/18 started adjuvant CT. 12/13 completed adjuvant CT. Four post-op deaths, all from ARDS, for a total of 7 deaths on study. 2/7 pts with pCR died, both of ARDS. With small numbers, the use of IMRT did not correlate with ARDS, but analysis of dosimetry is ongoing. Data updated 010610. Conclusions: This regimen demonstrated promising activity based on pCR rate. Toxicity was significant, leading to closure after stage I. All post-op deaths were due to ARDS. Investigation of ARDS cause is ongoing. Correlative studies underway. This regimen is not recommended. No significant financial relationships to disclose.