Intravenous Cereport (RMP-7) enhances delivery of hydrophilic chemotherapeutics and increases survival in bats with metastatic tumors in the brain

Purpose. The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain. Methods. Autoradiography and scintillation were used to examine uptake of t he lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemolherapeutic agents, as well as the large hydrophilic marker, 70 kDa d extran. Cereport was also tested in combination with the chemotherapeutic d rugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if C ereport could enhance the survival benefit beyond that provided by chemothe rapy alone. Results. Cereport enhanced the uptake of carboplatin and dextran, but not p aclitaxel or carmustine. The pattern of Cereport's uptake effect with carbo platin revealed that Cereport selectively increased the proportion of highl y permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carm ustine, compared to each chemotherapeutic agent alone. Conclusions. These data provide the first evidence that Cereport, or any re ceptor-mediated approach intended to enhance the permeability of the blood- brain tumor barrier, can increase the delivery hydrophilic drugs to metasta tic tumors in the brain, increasing survival in tumor-bearing rats.