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

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). 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, 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, AUC, and AUC. The safety profiles and anti-tumor effects were also determined. 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 values for ANX and Navelbine were 1,317.40 and 1,446.30 ng/mL, respectively. Corresponding AUC values were 797.08 and 924.26 ng·h/mL, respectively. AUC 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, 86.92% (90% CI, 80.91-93.37%) for AUC, and 87.44% (90% CI, 82.08-93.16%) for AUC. 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. At therapeutic dosage levels, pharmacokinetic behavior and safety profiles were similar for both formulations. Chinese National Registry Code: ChiCTR-IPR-15005856.