Nimotuzumab Combined With Concurrent Chemoradiation Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

Abstract

Concurrent chemoradiotherapy is the standard care in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC) with unsatisfied outcomes. Epidermal growth factor receptor (EGFR) overexpression occurred in 30-90% of esophageal cancers. Nimotuzumab, an inhibitor of EGFR, was effective in treating ESCC with mild toxicities in previous studies. To investigate the feasibility and efficacy of Nimotuzumab combined with concurrent chemoradiotherapy in unresectable locally advanced ESCC, we designed this study. The enrollment criteria included pathologically or cytologically diagnosed as ESCC, with untreated stage III disease according to AJCC 6thstaging system, ECOG performance score 0-2, unresectable disease. All of the enrolled patients received thoracic radiation with dose of 50-70Gy, Nimotuzumab 200mg per week and platinum/fluorouracil based chemotherapy, concurrently. The overall survival (OS), progression free survival (PFS) and local-regional free survival (LRFS) were calculated using the Kaplan-Meier method. Toxicities were evaluated according to the NCI-CTC 3.0. Response was assessed 1 month after treatment, according to Response Evaluation Criteria in Solid Tumors 1.0. From May 2011 to March 2015, 26 patients were enrolled. Twenty-three were male and 3 were female. The median age was 55.5 years. The disease was stage II, III, IV in 5, 14 and 7 patients , respectively. All patients were treated with concurrent chemoradiotherapy and Nimotuzumab. The median dose of radiotherapy was 60Gy (42-70Gy). Platinum plus paclitaxel, fluorouracil plus platinum, platinum alone and fluorouracil alone were given in 16 patients , 5 patients, 4 patients and 1 patients , respecitively. The median total dose of Nimotuzumab was 1200mg (200mg/week * 6weeks). At one month post-radiotherapy, there were 20 (76.9%) partial response, 4 (15.4%) stable disease and 2 (7.7%) progression disease. The median follow up time was 30.5 months. The median survival time was 28.7 months. Two- year and 3- year OS were 53.4% and 38.2%, LRFS were 73.3% and 62.8%, PFS were 46.2% and 33.3%. The incidence of grade 3-4 esophagitis, grade 3-4 digestive toxicities, grade 3-4 hematological toxicities, grade 3 skin dermitis and grade 2 pneumonitis were 61.5%, 7.7%, 26.9%,11.5% and 7.7%, respectively. Concurrent Nimotuzumab and chemoradiotherapy is effective and tolerable in locally advanced ESCC patients who are unfit for operation. Further evaluation based on larger cases is needed.