Therapeutic Effects Of Etoposide Implants On Lewis Lung Cancer

Objective:To prepare etoposide(VP-16)implants and to compare the effect of VP-16 implants on tumor growth,local recurrence and systemic toxicity with VP-16 solution.To discuss the advantages of VP-16 implants compared to VP-16 solution.Method: ? Prepare the implants using hot-melt extrusion and determine the cumulative release rate of etoposide-loaded implants in vitro and in vivo by HPLC method.? Establish the Lewis lung cancer(LLC)xenografted model by injecting LLC cells and compare the effect of VP-16 implants on tumor growth,survival time,body weight and organ index with VP-16 solution.? Establish tumor local recurrence model by local injecting LLC tumor tissue suspension and compare the effect of VP-16 implants on local recurrence,myelosuppression and liver injury with VP-16 solution.Result: The drug content of VP-16 implants was 37.62% with a continuous sustained release over 15 days from etoposide-loaded implants in vitro and in vivo.The VP-16 implants can inhibit tumor growth and prolong survival time significantly without influence on body weight and organ index.It is worth mentioning that the tumor inhibition rate of high dose(2.4mg)VP-16 implants was 70.96%(p < 0.001)and the survival time extending was over 100%.Intratumoural injection of VP-16 implants prevented local recurrence and decreased the myelosuppression and liver injury significantly compared with intraperitoneal injection of VP-16 solution.Conclusion: Local chemotherapy using VP-16 implants could increase the drug efficacy and decrease systemic toxicity.