A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with T4 esophageal cancer: Japan Clinical Oncology Group trial (JCOG 9908)

Background Nedaplatin is an analogue of cisplatin with less nonhematologic toxicity. The combination of nedaplatin and 5-fluorouracil showed a promising response rate in a previous phase II study for metastatic esophageal cancer. The purpose of this study was to determine a recommended dose and to evaluate the efficacy of nedaplatin and 5-fluorouracil combined with concurrent radiotherapy.Methods Eligibility criteria included squamous cell carcinoma of the thoracic esophagus; T4 disease without distant organ metastasis; age 20–70 years; performance status 0–2; and adequate organ functions. Patients received two cycles of nedaplatin (80 mg/m² or 90 mg/m²) on day 1 and continuous infusion of 5-fluorouracil 800 mg/m²/day on days 1–5, every 5 weeks with concurrent radiotherapy 60 Gy in 30 fractions.Results Between December 1999 and April 2002, 26 patients were accrued. The recommended dose of nedaplatin was 90 mg/m². Common grade ≥3 toxicities included leukopenia 9, neutropenia 5, thrombocytopenia 4, esophagitis 4, and esophageal fistula 3. Three of 26 patients achieved complete response (12%; 95% confidence interval, 2%–30%). With a minimum follow-up of 26 months for surviving patients, the median survival time was 12 months (95% confidence interval, 9–22 months), and the 2-year overall survival was 31% (95% confidence interval, 13%–49%).Conclusions This combined therapy is active with acceptable toxicity, however, the survival figure remains poor. Further investigation into more effective treatment is needed.