Safety results of a phase 3 study of comparing paclitaxel plus 5-fluorouracil versus cisplatin plus 5-fluorouracil in chemoradiotherapy for locally advanced esophageal carcinoma (ESO-Shanghai 1).

Abstract

4066 Background: Concurrent chemoradiotherapy (CCR) with cisplatin plus 5-Fu (PF) regimen is the standard modality for inoperable locally advanced esophageal squamous cell carcinoma (ESCC) patients. In this phase 3 trial, we aimed to assess the efficacy and safety of the paclitaxel plus 5-Fu (TF) regimen versus PF regimen in CCR for ESCC patients. Methods: ESCC patients presented with stage IIa to IVa were enrolled in a prospective multicenter phase 3 study. Patients were randomized to either PF group or TF group. Patients in PF group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with PF (cisplatin 25 mg/m2/d, d1-3, plus 5-Fu 1800 mg/m2, civ 72h, q28d). Patients in TF group were treated with 5 cycles of weekly TF (5-Fu 300 mg/m2, civ 96h plus paclitaxel 50 mg/m2, d1) in CCR followed by 2 cycles of monthly TF (5-FU 1800 mg/m2, civ 72h, plus paclitaxel 175 mg/m2 d1) in consolidation chemotherapy. The radiotherapy dose in both groups was 61.2 Gy delivered in 34 fractions. Adverse events (AE) defined according to CTCAE 4.0. The primary end-point was 3-yr OS. The number and grade of participants with AE was analyzed by intention to treat. Results: Between April 2012 and July 2015, 436 ESCC patients in 7 centers were enrolled. TF group had a significant higher incidence of acute Grade 3/4 leukopenia (31.3% vs. 18.9%), hiccup (0.9% vs. 0.0%), dermatitis (17.5% vs. 7.5%), pneumonitis (9.8% vs. 2.3%), and esophagitis (6.0% vs. 3.2%), and lower incidence of anemia (0.5% vs. 1.9%), thrombocytopenia (0.5% vs. 13.8%), fatigue (5.6% vs. 17.3%), anorexia (0.5% vs. 14.1%), nausea (0.5% vs. 14.1%), and vomiting (0.9% vs. 17.7%) than PF group (P < 0.05). There were 3(1.4%) patients in TF group died of acute pneumonitis. For long-term AE, 1(0.5%) patient in each group died of pneumonitis. There was no significant difference in total numbers of incidence of ≥ Grade 3 AE between two groups. Until Jan 2017, the median survival has not reached. Conclusions: The safety results of this trial were acceptable. TF regimen showed a different AE profile compared with PF regimen used in CCR in ESCC patients. Clinical trial information: NCT01591135.