A randomized phase II/III study of paclitaxel/cisplatin versus cisplatin/5-fluorouracil in neoadjuvant chemoradiotherapy (CRT) followed by surgery for patients with locally advanced esophageal squamous cell carcinoma (ESCC).

TPS4650 Background: Meta-analyses have shown the survival benefit of cisplatin/5-fluorouracil (PF) neoadjuvant CRT over surgery alone for patients with locally advanced ESCC. The CROSS study has demonstrated the statistically significant survival benefit of paclitaxel/carboplatin neoadjuvant CRT for patients with locally advanced esophageal cancer, especially ESCC. A network meta-analysis based on published phase III trials suggested that paclitaxel/platinum might be superior to PF as neoadjuvant CRT in patients with ESCC (Huang et al: Jpn J Clin Oncol. 2015;45:1023–8). However, a direct comparison of two CRT regimens in a prospective randomized clinical trial has not been performed in ESCC. We designed this clinical trial to test the hypothesis that paclitaxel-platinum is superior to PF as neoadjuvant CRT in patients with locally advanced ESCC. Methods: This single center open-label phase 2/3 study randomizes patients with histologically confirmed ESCC, T3/4aN0M0 or T1-3N1-3M0 (AJCC 7 th edition), in 1:1 ratio, to receive TP (paclitaxel, 50 mg/m2/week; cisplatin 30 mg/m2/week; for 5 weeks) or PF (cisplatin 75 mg/m2, d1; 5-FU 1,000 mg/m2, d1-4; on week 1 and week 5)-neoadjuvant CRT (180 cGy/d, 5 days/week, for 5 weeks). Esophagectomy will be performed 6 to 10 weeks after completing CRT. All patients must be eligible to esophagectomy, with tumor length ≤8cm and tumor radial ≤5cm, with adequate organ functions, and have ECOG performance status of 0-2. In the phase 2 stage, 128 patients will be enrolled, assuming the pathologic complete response (pCR) rate of TP and PF as 45% and 25%, respectively, with a power of 80% and one-sided 10% significance level. If the primary endpoint of pCR is met, additional 120 patients will be enrolled for the phase III stage with overall survival as the primary endpoint, assuming the hazard ratio of TP versus PF as 0.65 with a power of 80% and a 5% significance level. The trial started patient enrollment in May, 2017. As of Jan of 2020, 52 of planned 128 patients for phase II part have been enrolled. Clinical trial information: NCT03623737 .