Paclitaxel administration along with antiangiogenic therapy in hnscc xenograft model

At the conclusion of this presentation, the participant should be able to identify the additive therapeutic effects combining Paclitaxel and TNP-470 in head and neck cancer. Angiogenesis is essential for tumor growth and progression. In head and neck cancer a tight correlation for angiogenesis and tumor progression has been demonstrated. The study was conducted to evaluate if there are additive therapeutic effects combining Paclitaxel with the angiogenesis inhibitor TNP-470 in a mouse model for head and neck cancer. NMRI nude mice were inoculated with HNSCC-001 cell line. After 4 weeks of tumor establishment 4 mice were injected with TNP-470 s.c. (30 mg/kg) and Paclitaxel i.p (25 mg/kg) every other day for 12 days while 4 control mice received vehicle injections only. The tumor volume and body weight was measured every other day up to day 15, when all mice were sacrificed. Significant differences in tumor volume could be seen at day 8 of treatment. On day 15 of tumor volume was 739 ± 60 mm3 in the vehicle-treated group and 136 ± 55 mm3 in the TNP-470/Paclitaxel treated group (p=0,00001). The T:C ratio decreased gradually during the experiment, from 1,2 before treatment to 0,4 on day 15 when the animals were sacrificed. Neither in treatment nor in control group metastasis could be detected macroscopically and in histological examination. On day 15 the body weight in the control group was 22,3 ± 2,5 g and 30,8 ± 3,5 g in the TNP-470/Paclitaxel group (p=0,008). Previous studies have demonstrated that taxanes can decrease tumor progression. By the combination of TNP-470 and Paclitaxel the tumor growth was repressed in mice. Further investigation of this combination is warranted. Keywords: TNP 470, Paclitaxel, xenograft model, nude mice, head and neck cancer, squamous cell carcinoma, angiogenesis