Concomitant vinorelbine and radiation in head and neck squamous cell carcinoma in vitro

Abstract

Concomitant chemoradiotherapy has been used for locally advanced head and neck squamous cell carcinoma (HNSCC) particularily with cisplatin, 5-FU, methotrexate, bleomycin and taxanes. Vinorelbine is a semisynthetic vinca alcaloid, which causes a block in the G2/M phase of the cell cycle. HNSCC cell lines have previously been reported to be sensitive to vinorelbine in nanomolar concentrations. In the current study the effect of vinorelbine as a radiosensitizer in vitro was studied and eight recently established head and neck SCC cell lines of the UT-SCC-series were tested. Vinorelbine concentrations of 0.4–1.6 nM were used, corresponding to the IC70, IC50 and IC30 values of each cell line, resulting in 30%, 50% and 70% inhibition in clonogenic survival. The desired concentrations of vinorelbine were added to the medium and the cells were plated in 96-well culture plates in this solution. The plated cells were irradiated 24 h later with 4MeV photons generated by a linear accelerator and incubated at 37°C with 5% CO₂ for 4 weeks. Thereafter, the number of wells containing coherent, living colonies, consisting of 32 cells or more, was counted. The plating efficiency was calculated and the fraction survival data were fitted to the linear quadratic model [F=exp[−(αD+βD²)]]. An additive effect of combining vinorelbine and irradiation could be demonstrated. The dose-dependent decrease in survival was seen at vinorelbine doses of 0.4–1.6 nM in all cell lines tested.