BACKGROUND: There is an urgent need for an effective second-line chemotherapy regimen after failure of the standard cisplatin and 5-fluorouracil therapy. PATIENTS AND METHODS: This study investigated the efficacy and toxicity of the combination of docetaxel (30 mg/m) during a 1-hour infusion, followed by nedaplatin (50 mg/m) during a 2-hour infusion (both drugs were administered on day 1 as an outpatient regimen and repeated every 2 weeks) as second-line chemotherapy for patients with cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma after surgery. RESULTS: Forty-six of the 48 patients (95.8%) were assessable for response. Partial response was confirmed in 13 of 48 cases yielding a response rate of 27.1% (95% confidence interval [CI], 14.5-39.7%). The median overall time to progression and overall survival was 3.1 months (95% CI, 2.3-3.9 months) and 5.9 months (95% CI, 3.9-7.8 months), respectively. The estimate of overall survival at 12 months was 16.7% (95% CI, 6.1-27.2%). Grade 3 anemia leucopenia, grade 4 anemia leucopenia and neutropenia were detected in only 4 (8.7%), 8 (17.4%), and 9 patients (19.6%), respectively. CONCLUSIONS: The combination chemotherapy of docetaxel and nedaplatin in the outpatient setting is well tolerated and useful as second-line chemotherapy for cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma. © 2009 International Association for the Study of Lung Cancer.