Therapeutic effect of gemcitabine on experimental tumors of the brain.

Abstract

e13005 Background: Gemcitabine has a very modest potency to penetrate blood-brain barrier (BBB). So far it's therapeutic activity in intracranial tumors is unknown. Methods: we explored the effect of gemcitabine (G) on overall survival in models of intracranial Ehrlich's tumor and lymphosarcoma LIO-1. As a comparison for the investigation group we've chosen drugs with different ability to penetrate into brain. We injected BCNU (50 mg/kg), cyclophosphamide (C) (150 mg/kg) and CDDP (9 mg/kg) intraperitoneally once 24 hours after transplantation. Results: The mean overall survival (OS) of mice in a selected model is 9,6+/-0,4 days. The injection of G resulted in substantial increase in OS up to 16,2 +/-0,4 (69%, p = 0,0000). In comparative groups administration of BCNU resulted in an increase in OS of 49% (the average OS 14,3+/-0,8, p = 0.000289), C - in 20% OS increase (11,5+/-0,4, p = 0.00272) and CDDP did not influence OS comparing with control group (10,2+0,4 days, p = 0.315). In other experiment mice with intracranial transplantated lymphosarcoma LIO-1 lived 15.4+1.3 days after single i.p. administration of G (25 mg/kg in 24 hours after transplantation) in comparison with 11.2+0.4 days in control group. The absolute increase of life expectancy was 37.5% (p = 0.013). In control group at 14 day after the transplantation all animals died whereas in G group only 3 mice out of 10 (30 %, g = 0.0003) died. Single i.p. administration of 25 mg/kg G on the 5th day after the intracranial transplantation of LIO-1, increased average OS of the animals from 10,9+ 0,4 days in control group to 13.5±0.5 days (increase in OS 24%, p = 0.0003). Conclusions: In our series of experiment we showed the potency of gemcitabine in treatment of various intracranial tumors. Until our work we can not find any data obtained on efficacy of gemcitabine in this tumor types.