Comparison of intravenous versus intracarotid therapy with @entity3600 in a @entity35 XXXX model.

@entity3038 @entity137 @entity1313 @entity5 @entity11 @entity3600 @entity35
Currently numerous clinical trials are in progress utilizing intracarotid (i.c.) @entity3600 (BCNU) for the treatment of @entity11 based upon the proposed focal nature of these @entity5 and the assumption that the i.c. route delivers higher levels of drug to the @entity5 . To date, however, increased efficacy in an animal model has not been clearly demonstrated for the i.c. delivery of BCNU. We have evaluated the dose-response curve for the i.v. and i.c. administration of @entity3600 in a commonly utilized experimental @entity1313 model, the 9L @entity35 @entity3038 . An initial @entity137 trial utilizing the i.p. 10% lethal dose (LD10) of BCNU by the i.v. and i.c. routes failed to demonstrate any significance in @entity137 between the two routes. Tumor-bearing animals were then treated on Day 15-16 after @entity5 inoculations with 1, 10, 25, 50, 75, and 100% of the LD10 dose by either the i.v. or the i.c. route. Both i.v. and i.c. BCNU gave maximum survival increases at 75-100% LD10 doses, and there was no therapeutic advantage seen from i.c. delivery. However, at 50% of the LD10 dose (6.65 mg/kg), triplicate experiments demonstrated that the i.c. but not the i.v. dose maintained maximum efficacy equivalent to 100% of the LD10 given either i.v. or i.c. When the dose was reduced to 25% of the LD10 dose (3.33 mg/kg), two of three experiments showed efficacy of the i.c. delivery of this lower drug dosage to be equivalent to 100% of the LD10 given i.v. or i.c. The i.v. dosage resulted in a significant reduction in survival in all three trials. At 10% of the LD10 dose (1.30 mg/kg), neither the i.v. nor the i.c. administration retained equivalent efficacy to 100% of the LD10. However, in one of two trials, the i.c. groups had statistically better survival than controls, while in neither experiment was any advantage over controls seen in the i.v. treated groups. At 1% of the LD10 dose, neither the i.v. nor the i.c. route demonstrated any therapeutic efficacy. From our data, the advantage of the i.c. delivery of BCNU in the intracranial 9L @entity35 @entity3038 appears to be in the fact that significantly lower dosages than those given i.v. may be utilized to achieve equivalent survival with potentially less systemic @entity137 .
