Pulmonary distribution of vinorelbine in patients with non-small-cell lung cancer

Abstract

Vinorelbine (Navelbine, NVB) is a new semi-synthetic vinca alkaloid that is currently used in the treatment of advanced breast cancer and advanced non-small-cell lung cancer (NSCLC). In this study we investigated the tumoral and healthy pulmonary tissue concentrations of NVB in previously untreated NSCLC patients undergoing surgery. A total of 13 patients (mean age, 60 years; range, 42-70 years) were included and received NVB (20 mg/m2) at 1 h (mean, 1.1 h; SD, 0.2 h; n = 6 patients) and 3 h (mean, 3.0 h; SD, 0.6 h; n = 7 patients) before tumor resection. A tumoral and adjacent healthy lung-tissue specimen as well as simultaneously sampled serum were analyzed for NVB by high-performance liquid chromatography (HPLC). NVB levels were much higher in tissue than in serum (up to 300-fold). The tissue/serum ratio increased between the 1-h sampling time (range, 0.1-100) and the 3-h time point (range, 10-300). In all patients but two, NVB concentrations were lower in tumors than in healthy lung tissue. The tumor/healthy tissue ratio ranged from 0.06 to 1.3 (median, 0.09) at 1 h and from 0.18 to 1.1 (median, 0.55) at 3 h. This ratio increased between the 1-h sampling time and the 3-h time point as a consequence of increasing tumor levels (median, 50.4 ng/g at 1 h and 278 ng/g at 3 h). In four patients, concentrations could be measured in necrotic and peripheral tumor zones, showing lower values in necrotic areas. Thus, these data indicate that NVB is highly distributed in lung tissue, with the disposition rate being slower in tumor tissue than in healthy parenchyma during the first 3 h.