Phase II trial of combination therapy using S-1, cisplatin, and radiation for distant metastatic esophageal cancer (stage IVb).

e14596 Background: S-1 is an orally active fluoropyrimidine that enhances the efficacy of radiotherapy (RT) and has low gastrointestinal toxicity. Our previous phase II study demonstrated that definitive chemoradiotherapy (CRT) with S-1 and cisplatin was well-tolerated and had favorable activity for locally advanced esophageal cancer (Iwase H et al, Proc. ASCO 2011, Abst 4034). The present study was a phase II trial of combination therapy using S-1, cisplatin, and RT for distant metastatic esophageal cancer (DMEC). Methods: S-1 (80 mg/m2/day) was given orally for 14 consecutive days from Day 1 and cisplatin (70 mg/m2) was administered on Day 14, both with 3 weeks of RT (2.0 Gy per traction) 5 times per week for the primary lesion and metastases in the neck, which initiated on Day 1. One Cycle equals 5 weeks, 2 weeks of chemotherapy concurrent with 3 weeks of RT followed by 2 weeks of complete rest. After 2 cycles, only chemotherapy with S-1 and cisplatin were administered. Results: Forty-one patients with DMEC (Stage IVb) were enrolled between March 2002 and February 2011. 37/male7/female, median age 67.5 years (48-82). The median survival follow-up time was 16.6 months and 37 patients (90.2%) completed the combination treatment. The most common adverse event was neutropenia. Grades 3 and 4 neutropenia were observed in 29.2% and 12.2%, respectively. In general, non-hematological adverse events were mild and the most common were Grade 2 nausea (34.1%), esophageal pain and oral mucositis (17.1% each), and renal dysfunction (9.8%). The overall response rate was 65.9% comprising 93.2% in the primary lesion, 60% in the liver metastasis, 64.3.% in the lung, 54.5% in the distant lymph node, 83.3% in the regional lymph node metastasis, and 50% in the other distant metastases. Thirty-nine patients (88.6%) showed improvement in their dysphagia score. The median progression-free and overall survival durations were 5.3 [95% confidence interval (CI), 4.1 to 6.0] and 13.1 months (95% CI, 9.8 to 15.6), respectively. Conclusions: Combination therapy using S-1, cisplatin, and RT has a promising safety and efficacy profile. Potentially, this regimen could become the baseline treatment for patients with DMEC.