Long-term follow-up of a randomized phase II study of Cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021)

Objective: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. Methods: Eligible patients were ,75 years old and performance status 0–2, and had Stages II–IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m 2 Days 1 and 29 and 5-fluorouracil 700 mg/m 2 Days 1–5 and 29–33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m 2 Days 1 –5 , 8 –1 2, 29 –3 3 and 36 –4 0, and 5-fluorouracil 250 mg/m 2 Days 1 – 14 and 29 – 42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. Results: Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22–48%), while those for arm B were 44 and 22% (11–35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. Conclusions: Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.