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 μl/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.