PURPOSE: We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer. METHODS: We performed a phase I dose-escalation trial of docetaxel at 25-40 mg/m(2) in four planned dose levels in 3-6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70 mg/m(2) on days 1 and 29) and 5-fluorouracil (70 mg/m(2)/day on days 1-4 and 29-32) and concurrent radiation therapy (40 Gy). The tumors were resected during weeks 10-13. RESULTS: This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30 mg/m(2) when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25 mg/m(2). Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications. CONCLUSIONS: This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.
PURPOSE: We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer. METHODS: We performed a phase I dose-escalation trial of docetaxel at 25-40 mg/m(2) in four planned dose levels in 3-6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70 mg/m(2) on days 1 and 29) and 5-fluorouracil (70 mg/m(2)/day on days 1-4 and 29-32) and concurrent radiation therapy (40 Gy). The tumors were resected during weeks 10-13. RESULTS: This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30 mg/m(2) when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25 mg/m(2). Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications. CONCLUSIONS: This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.