A phase II study of radiotherapy combined with docetaxel, cisplatin, and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer.

Abstract

4029 Background: Recently, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery for patients with esophageal cancer have resulted in favorable prognosis, but extended radical esophagectomy with two-field or three-field (neck, mediastinum, and abdomen) lymph node dissection remains a standard treatment. However, there is recurrence in 30-50% of patients who have undergone an operation and there is loco-regional recurrence in 40-55% of patients with postoperative recurrence. The efficacy and safety of chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer have been reported, and the survival outcome has been improved; however, the median progression-free survival period according to past reports was 10 to 14 months, which was not enough. Recently, RT with docetaxel (DOC), cisplatin (CDDP) and 5-FU has shown better results than conventional standard treatment (CDDP+5-FU +radiotherapy) for primary esophageal cancer. The purpose of the phase II study was to evaluate the superior of definitive radiotherapy with DOC, CDDP and 5-FU to the standard treatment in patients with loco-regional recurrent esophageal cancer after curative resection. Methods: Between 2015 and 2023, this open-label, single-arm, phase II study of radiotherapy (60 Gy/30 fractions/6 weeks without prophylactic region) combined with chemotherapy consisting of 3 cycles of DOC (35 mg/m2), CDDP (40 mg/m2) and 5-FU (400 mg/m2/24 h for 5 days) for patients with postoperative loco-regional recurrent esophageal cancer was conducted at a single institution. The primary endpoint was progression-free survival rate. This trial was considered positive if median progression-free survival period was 24.0 months or more, which meaning superiority over conventional standard treatment. The secondary endpoints were overall survival rate and adverse events. This trial was registered with UMIN Clinical Trials Registry (UMIN000019269) and Japan Registry of Clinical Trials (jRCTs021200009). Results: A total of 29 patients were enrolled in this study. The regimen was completed in all the patients. The median observation period for survivors was 60 months (IQR, 30.0-75.5 months). The 5-year progression-free survival rate was 56.2% (95% CI = 37.4-75.0%) with a median progression-free survival period of 62.0 months (95% CI = 35.2-64.7 months). Only 2 patients showed grade 4 hematologic adverse events during chemoradiotherapy, and they had to be performed reduced chemotherapy; however, they also completed 3 cycles of concurrent chemotherapy. Grade 2 or higher late toxicity was not observed in any patients. Conclusions: The present protocol of radiotherapy combined with DOC, CDDP and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. It might be better than conventional treatment. Clinical trial information: UMIN000019269.