Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in XXXX .

@entity1 @entity2656 @entity1158 @entity4174 @entity64 @entity410 @entity39 @entity1269 @entity5 @entity16 @entity1221 @entity786 @entity51 @entity1499 @entity463
Reversible osmotic blood-brain barrier (BBB) modification was used in 38 @entity1 with @entity463 to enhance the delivery of chemotherapeutic agents. The @entity1 ranged in age from 14 to 70 years (mean, 43), and all had prior surgery and radiation; 5 had also received systemic chemotherapy. Karnofsky Performance Status (KPS) scores ranged from 60 to 100% (mean, 79) on admission to the treatment program. Barrier modification was achieved by intracarotid or intravertebral artery infusion of @entity2656 , and a chemotherapy regimen of @entity1499 , @entity786 , and @entity4174 was given in conjunction with barrier modification. The 38 @entity463 @entity1 were compared to two control groups of @entity1 with @entity463 ; these encompassed 14 @entity1 treated with surgery and radiation and 8 treated with surgery, radiation, and systemic chemotherapy. Survival analysis using the Cox Proportional Hazards Regression Model (corrected for age, sex, presence or absence of @entity39 , and functional status) showed that @entity1 receiving chemotherapy with BBB modification had a statistically significant (P = 0.0006) longer expected survival (17.5 months) than the control groups (12.8 and 11.4 months, respectively). Presently 16 @entity1 of the barrier-enhanced treatment group are alive at 5 to 42 months from diagnosis (median, 20) with KPS scores ranging from 40 to 90% (median, 65). The @entity16 seen included @entity64 in 3 @entity1 (1 with decreased motor movement in the hand, 1 with marked @entity1269 , and 1 with @entity1158 ), transient exacerbation of preexisting @entity51 lasting 2 to 3 days, and a 15% incidence of @entity410 during or within 24 hours of the BBB modification. In 2 of the 38 @entity1 , @entity1221 regression concurrent with the development of new @entity5 nodule(s) in portions of the brain distant from the region of osmotic BBB opening was seen. These studies indicate that chemotherapeutic drug delivery to @entity5 (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival.
