Prospective Randomized Phase 2 Study of Concurrent Chemoradiation Therapy (CCRT) Versus Chemotherapy Alone in Stage IV Esophageal Squamous Cell Carcinoma (ESCC)

Abstract

Stage IV ESCC carries a poor prognosis with a median survival of 6-9 months. The standard treatment has traditionally been chemotherapy. Palliative radiation therapy was used for symptom relief. The optimal treatment for stage IV ESCC has not yet been established. The aim of this study was to compare the efficacy and safety of CCRT versus chemotherapy alone in patients with stage IV ESCC. Patients with stage IV ESCC were randomly assigned to the CCRT group and the chemotherapy group. Both groups of patients received at least 2 cycles of chemotherapy with cisplatin and docetaxel every 3 weeks. Patients in CCRT group received 50-60 Gy/ 25-30 fractions/ 5-6 weeks of concurrent radiation therapy to the esophageal primary tumor. The primary end point was overall survival (OS). The secondary end points were progression-free survival (PFS), object response rate (ORR) of primary tumor and toxicity. Between August 2013 and October 2015, 60 patients were enrolled and divided into the CCRT group (n = 30) and the chemotherapy group (n = 30). The 60 patients were comprised of 48 male and 12 female patients, with a median age of 56 years (range 36 - 70 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the CCRT group received a mean 54.7 Gy of radiation therapy and a mean 3.6 cycles of chemotherapy, whereas patients in the chemotherapy group received a mean 3.8 cycles. The ORR of the primary tumor was higher in the CCRT group than in the chemotherapy group (83.3% vs. 46.7%, P = 0.001). At a median follow-up of 18 months, median PFS (9.3 vs. 4.7 months, P = 0.021) and median OS (18.3 vs. 10.2 months, P = 0.001) were significantly longer in the CCRT than that in the chemotherapy group. Overall survival rates at 1and 2 years were 73.3% and 43.3% respectively, in the CCRT group, and 46.6%and 26.7% respectively in chemotherapy group (P = 0.030) Although ≥ grade 3 neutropenia was significantly more frequent in the CCRT group than that in the chemotherapy group (33.3% vs. 20.0%, P < 0.05), the rates of other toxicities did not differ. Concurrent chemoradiation therapy was well tolerated and associated with longer PFS and OS than chemotherapy alone in patients with stage IV ESCC. Controlled randomized, multi-center trials are required to determine whether CCRT is a primary treatment option for patients with stage IV ESCC.