Background: While neoadjuvant chemoradiation therapy (nCRT) with subsequent surgery is the treatment of choice for patients with locally advanced or node-positive squamous cell carcinoma of the esophagus (SCC) suitable for surgery, patients who are unsuitable for surgery or who refuse surgery should be treated with definite chemoradiation therapy (dCRT). Purpose of this study was to compare toxicity and oncologic outcome of dCRT with either cisplatin and 5-fluoruracil (CDDP/5FU) or carboplatin and paclitaxel (Carb/TAX) in patients with SCC.Methods: Twenty-two patients who received dCRT with carboplatin (AUC2, weekly) and paclitaxel (50 mg per square meter of body-surface area, weekly) were retrospectively compared to 25 patients who were scheduled for dCRT with cisplatin (20 mg/m(2)/d) and 5-fluoruracil (500 mg/m(2)/d) on day 1-5 and day 29-33. For the per-protocol (PP) analysis, PP treatment was defined as complete radiation therapy with at least 54Gy and at least three complete cycles of Carb/TAX or complete radiation therapy with at least 54Gy and at least one complete cycle of CDDP/5FU. While patients who were scheduled for dCRT with Carb/TAX received a significantly higher total radiation dose (median dose 59.4Gy vs. 54Gy, p < 0.001) than patients who were scheduled for dCRT with CDDP/5FU, no significant differences were seen for other parameters (age, sex, TNM-stage, grading and tumor extension).Results: Forty-seven patients (25 patients treated with CDDP/5FU and 22 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 41 of 47 patients (23 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. Severe myelotoxicity (>= III degrees) was seen in 52% (CDDP/5FU) and 55% of patients (Carb/TAX), respectively (p = 1.000). In the univariate binary logistic regression analysis, patients age was the only factor associated with an increased risk of >= III degrees myelotoxicity (hazard ratio 1.145, 95% CI 1.035; 1.266; p = 0.009). Regarding treatment efficiency, no significant differences were seen for overall survival (OS) and freedom from relapse (FFR) between both treatment groups.Conclusion: Myelotoxicity and oncologic outcome under dCRT were not different for patients with SCC of the esophagus treated with either CDDP/5FU or Carb/TAX. The putative equivalence of dCRT with Carb/TAX in this setting should be further investigated in prospective trials. However, our data reveal that the risk of significant myelotoxicity increases with patient age and therefore other chemotherapy regimens might be evaluated in elderly patients.