Concurrent chemoradiotherapy with cetuximab plus twice-weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal squamous cell carcinoma.

4099 Background: We investigated the efficacy and safety of adding cetuximab to twice-weekly paclitaxel/cisplatin-based concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with locally advanced ESCC (T3N0-1M0 or T1-3N1M0 or M1a by AJCC 2002) were treated with paclitaxel (35 mg/m 2 1 h D1, 4/wk), cisplatin (15 mg/m 2 1 h D2, 5/wk), cetuximab (400 mg/m 2 2 h D-5, then 250 mg/m 2 1 h D3/wk) and radiotherapy (2 Gy D1-5/wk). The feasibility of esophagectomy was evaluated for all patients at the accumulated radiation dose of 40 Gy. If esophagectomy was not feasible, CCRT was continued to a radiation dose of 60-66 Gy. Results: 66 patients were enrolled between Oct 2008 and Jun 2010, and 61 (94%) of them had T3N1M0 or M1a tumors by endoscopic ultrasonographic staging. All patients received CCRT to 40 Gy. Forty-three patients underwent surgery, and 17 patients continued definitive CCRT to 60-66 Gy. Of the scheduled doses of paclitaxel, cisplatin, and cetuximab, 80%, 79%, and 99% were given, respectively. The most common grade 3/4 toxic effects were leukopenia (51%), neutropenia (15%), esophagitis (19%), and infection (12%). The pathological complete response rate was 24% (intent-to-treat, 16/66) (95% confidence interval: 13-35%) and 37% (who underwent resection, 16/43). At the median follow-up of 34.6 months, the median progression-free (PFS) and overall survivals were 21.6 and 33.9 months, respectively. No KRAS codon 12/13 mutations were identified in 47 tumor samples. The median PFS for patients with two, one, and no adverse tumor biomarkers (Tau+, ERCC1+, pEGFR-) (n = 40) was 12.3 months, 27.6 months, and greater than 33.6 months, respectively (p = .087). Conclusions: Adding cetuximab to twice-weekly paclitaxel/cisplatin-based CCRT prior to esophagectomy is an active and tolerable treatment for locally advanced ESCC. Clinical trial information: NCT01034189. [Table: see text]