New approach to tumor therapy for inoperable areas of the brain: chronic intraparenchymal drug delivery.
Because the brainstem has little functional redundancy, diffuse lesions have been regarded as inoperable. To determine whether local drug therapy can prolong survival in a rodent model of a tumor in such eloquent tissue, lethal doses of F98 and 9L tumor cells were injected into the brainstems of Fischer 344 rats. Five days after inoculations, 0.5 mg/ml solutions of carboplatin were infused at 1 microl/h for 7 days. Compared to control groups that survived 13-17 days with F98 tumors and 22-23 days with 9L tumors, animals locally infused with 0.1 mg of carboplatin survived 27-30 days (Prob > Chi Sq = 0.0003), and 32 days (Prob > Chi Sq = 0.01), respectively. Measurements of tissue platinum levels at autopsy suggested that infusions distributed pharmacologically relevant levels of carboplatin through a volume of tissue at least 0.5 cm in diameter. The results suggest that chronic low-flow infusions provide a promising approach to therapy for CNS lesions in tissues considered to be inoperable.
Carson
Benjamin S
BS
Johns Hopkins Neurological Surgery and Hunterian Brain Tumor Laboratories, Baltimore, MD 21287-8811, USA.
Wu
Qingze
Q
Tyler
Betty
B
Sukay
Lindsey
L
Raychaudhuri
Ratul
R
DiMeco
Francesco
F
Clatterbuck
Richard E
RE
Olivi
Alessandro
A
Guarnieri
Michael
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016190:Carboplatin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D007260:Infusion Pumps; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis
D000970:Antineoplastic Agents; D016190:Carboplatin