This phase I study was designed to determine the maximum-tolerated dose (MTD) of docetaxel (TXT) and toxicities of combining weekly administration of TXT and continuous infusion of 5-fluorouracil (5-FU) with concomitant radiotherapy for advanced esophageal cancer.
Patients and methods: Patients received TXT by i.v. infusion over 1 h on days 1, 8, 22 and 29. They were also given 5-FU 250 mg/m2/day by continuous infusion for 24 h on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45. Fractionated radiotherapy was performed on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45, and a total dose of 60 to 66 Gy was delivered. The starting dose level (Level 1) of TXT was set at 7.5 mg/m2. Dose escalation was conducted in increments of 25 mg/m2, until the dose reached Level 4 (15 mg/m2). At least three patients were enrolled at each level.
Results: Seven patients (median age, 64 years) were enrolled. Six patients had stage III (T4NIMO) and one had stage IVb (T4N1M1b) esophageal cancer; six had squamous cell carcinoma and one had carcinosarcoma. No patient had received prior chemotherapy or radiotherapy, and two patients had undergone esophageal bypass surgery using a whole stomach tube without resection of primary or metastatic lesions. In the 7patients, the regimen was well-tolerated, with esophagitis as the most common toxicity (grade 3: n=1; grade 4: n=3). In general, hematological toxicity was mild. Dose-limiting toxicity (DLT) was observed at Level 2 (TXT 10 mg/m2) when three patients developed grade 4 esophagitis and this dose was deemed the MTD for this regimen. In the 7 assessable patients, the overall clinical response rate was 85.7%.
Conclusion: The MTD of TXT in this regimen was 10 mg/m2 and the recommended dose of TXT was 7.5 mg/m2. Although esophagitis was the dose-limiting and the most frequent toxicity, the regimen was safe and well-tolerated, and demonstrated the possibility of good efficacy in patients with advanced esophageal cancer.