Comparing Paclitaxel/5-Fluorouracil Versus Cisplatin/5-Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer (ESO-Shanghai 1): A Randomized, Multicenter, Phase III Clinical Trial

Background: This trial aimed to assess the efficacy and safety of the paclitaxel/5-fluorouracil (TF) regimen versus the cisplatin/5- fluorouracil (PF) regimen in definitive concurrent chemoradiotherapy (dCRT) for locally advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: Locally advanced ESCC patients were enrolled and randomized to either TF or PF group. The patients in the TF group were treated with 5 cycles of weekly TF in dCRT followed by 2 cycles of monthly TF in consolidation chemotherapy. The patients in the PF group were treated with 2 cycles of dCRT followed by 2 cycles of consolidation chemotherapy with monthly PF. The radiotherapy dose was 61·2 Gy delivered in 34 fractions. The primary end-point was 3-yr overall survival. Results: Four hundred thirty-six ESCC patients in 6 centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48·7 months (IQR 5·3-73·0). The 3-yr overall survival was 55·4% in the TF group and 51·8% in the PF group (HR 0·905, 95% CI 0·698-1·172, P=0·448). The TF group had significantly lower incidences of acute ≥ Grade 3 anemia (2·8% vs. 7·3%, P=0·030), thrombocytopenia (0·5% vs. 15·1%, P=0·000), anorexia (1·4% vs. 15·1%, P=0·000), nausea (1·4% vs. 14·6%, P=0·000), vomiting (2·3% vs. 18·7%, P=0·000), and fatigue (6·9% vs. 21·0%, P=0·000), and significantly higher incidences of acute ≥ Grade 3 leukopenia (31·3% vs. 18·3%, P=0·002), radiation dermatitis (5·1% vs. 1·4%, P=0·032), and radiation pneumonitis (8·8% vs. 2·7%, P=0·007) than the PF group. The long-term ≥ Grade 2 adverse events were similar between the two groups. Conclusions: Although the TF regimen did not significantly prolong the overall survival compared with the standard PF regimen, it might be another option to employ in dCRT for ESCC patients with lower incidences of severe thrombocytopenia, anemia and gastrointestinal toxicities. Clinical Trial Number: The study was registered with ClinicalTrials.gov, number NCT01591135. Funding Statement: The ESO-Shanghai 1 trial was supported by the National Natural Science Foundation of China, China (grant 81703160). The funder of this trial had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The protocol was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center (1203108-4). All participants provided written informed consent.