Abstract
PURPOSE: This open-label feasibility study assessed the tolerability of nintedanib 200 mg in combination with docetaxel 75 mg/m(2) as a starting dose in Japanese patients with a body surface area (BSA) < 1.5 m(2) and locally advanced or metastatic lung adenocarcinoma. METHODS: Eligible patients received docetaxel 75 mg/m(2) every 21 days and nintedanib administered at 200 mg twice daily (bid), starting on day 2 of each cycle. Treatment was continued until disease progression or undue toxicity. The primary endpoint was the number of patients experiencing dose-limiting toxicities (DLTs) in cycle 1 (days 1-21). RESULTS: Of 10 treated patients, 2 patients (20%) experienced DLTs during cycle 1. These DLTs were grade 3 liver enzyme elevations [alanine aminotransferase (2 patients) and aspartate aminotransferase (2 patients)], and grade 2 hyperbilirubinemia (1 patient). Nine patients met the predefined criteria for nintedanib 200 mg bid plus docetaxel 75 mg/m(2) to be considered a tolerable starting dose. All patients experienced ≥ 1 adverse event (AE) during the treatment period (all drug-related), but no patients experienced AEs that led to discontinuation of nintedanib. Of the five serious AEs reported during treatment, none were drug-related. There was no apparent effect of nintedanib on the pharmacokinetics of docetaxel. The objective response and disease control rates were 40 and 70%, respectively. CONCLUSION: Nintedanib 200 mg bid plus docetaxel 75 mg/m(2) is a tolerable starting dose in Japanese patients with a BSA < 1.5 m(2) with locally advanced or metastatic lung adenocarcinoma. CLINICALTRIALS. GOV NUMBER: NCT02300298.