A Phase I Comparative Pharmacokinetic and Safety Study of Two Intravenous Formulations of Vinorelbine in Patients With Advanced Non-Small Cell Lung Cancer

Purpose: The aim of this study was to compare the pharmacokinetics and safety between two vinorelbine formulations [a new oil-in-water emulsion formulation (ANX) versus a previously marketed solution formulation (Navelbine)] in Chinese patients with advanced non-small cell lung cancer (NSCLC). Method: This was a single-center, randomized, open-label study. Eligible patients aged 18–70 years who had histologically or cytologically confirmed NSCLC were enrolled. In cycle 1, the patients alternatively received the two formulations (30 mg/m(2), given as a 10-min infusion) with a 7-day interval. Samples for pharmacokinetic analysis were taken during cycle 1. For all subsequent 21-day cycles (maximum four cycles), ANX was administered on days 1 and day 8. Bioequivalence analysis was performed on C(max), AUC(last), and AUC(inf). The safety profiles and anti-tumor effects were also determined. Results: From March 2013 to January 2015, 24 patients were enrolled and 20 were eligible for pharmacokinetic evaluation. The 20 subjects in the pharmacokinetic analysis set had a median age of 61 years (range, 37–70 years), and 15 patients were male (75%). Mean vinorelbine C(max) values for ANX and Navelbine were 1,317.40 and 1,446.30 ng/mL, respectively. Corresponding AUC(last )values were 797.08 and 924.26 ng·h/mL, respectively. AUC(inf )values were 830.14 and 957.16 ng·h/mL, respectively. Treatment ratios of the geometric means were 90.00% (90% CI, 83.22–99.07%) for C(max), 86.92% (90% CI, 80.91–93.37%) for AUC(last), and 87.44% (90% CI, 82.08–93.16%) for AUC(inf). These results met the required 80–125% bioequivalence criteria. The most frequently reported adverse events after vinorelbine administration were neutropenia, leucopenia, neutropenic fever, and constipation. Conclusion: At therapeutic dosage levels, pharmacokinetic behavior and safety profiles were similar for both formulations. Chinese National Registry Code: ChiCTR-IPR-15005856.