Abstract
BACKGROUND: This phase I study aimed to assess the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin-bound (nab)-paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab-paclitaxel (60 mg/m(2) , 75 mg/m(2) , and 90 mg/m(2) ) and cisplatin (25 mg/m(2) ) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50-64 Gy. The primary endpoint was the safety of chemotherapy. RESULTS: The study enrolled 12 patients across three dose levels. No treatment-related deaths occurred. One patient in the 60 mg/m(2) dose level occurred dose-limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m(2) dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m(2) based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1-2 of 66.7% and Grade 3-4 of 33.3%), neutropenia (Grade 1-2 of 91.7% and Grade 3-4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%. CONCLUSIONS: Weekly schedule of cisplatin and nab-paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab-paclitaxel for further studies is 75 mg/m(2) .