Cetuximab, paclitaxel, cisplatin and concurrent radiation in Chinese patients with locally advanced esophageal squamous cell carcinoma: An open-label, multicenter, phase II study.

Abstract

4073 Background: In China more than 90% of esophageal malignancies are of squamous cell carcinoma (SCC). We conducted this Chinese multicenter trial to determine the efficacy and safety of the addition of cetuximab with paclitaxel, cisplatin, and concurrent radiation for patients with esophageal SCC and to determine whether KRAS status predicts response. Methods: Patients with unresectable locally advanced cervical, upper or mid-esophageal SCC without distant metastasis were eligible for this open-label phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation. The primary end point was response rate. Second end points included toxicity, overall survival (OS), progression-free survival (PFS), and KRAS mutation status. Results: Fifty-five patients were enrolled and evaluable to safety. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). Ten patients did not complete the protocol therapy (6 for chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the treating physicians for unstated reasons, 1 for concurrent unrelated infection, and 1 for tracheo-esophageal fistula). The response rate was 97.7%. The 1-year OS and median OS was 87.3% and 16.8 months, the 1-year PFS and median PFS was 30.4% and 13.9 months, respectively. No mutations were detected at KRAS codons 12 or 13 in the 52 available specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response.