Abstract
This abstract describes the use of surgically prepared tethered rats to evaluate the anti-tumour efficacy effects of a protein kinase inhibitor. Female nude rats were subcutaneously inoculated with HCT 116 human colon colorectal carcinoma cells, surgically implanted with indwelling femoral vein catheters and monitored for tumour growth. Following a suitable tumour growth period thirty two animals were allocated to 3 treatment groups (0.5, 1 and 2mg/kg/h) and a control group. The treatment regimen comprised of 2 cycles of 72 hours of continuous intravenous infusion at a rate of 4ml/kg/h followed by a 4 day post dose observation period. For comparative purposes, an additional 4 animals were allocated to a fifth group and dosed by daily intraperitoneal injection (50mg/kg/day) over 2 cycles. The reduction in tumour growth noted for animals dosed at 2mg/kg/h by continuous intravenous infusion was comparable to that of the animals dosed by intraperitoneal injection (50mg/kg). Reductions in neutrophils and reticulocytes were evident for animals in the treated groups 48 hours after dosing of the first cycle and evidence of recovery was noted prior to commencement of the second cycle. Tumour mass weights measured at necropsy showed a dose related reduction for animals dosed by continuous intravenous infusion.
