A multicenter phase II study of induction CT with FOLFOX-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC)

Abstract

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate. Results: Up to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35–70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patient's refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after > 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease. Conclusions: The current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.