TY - JOUR
T1 - New approach to tumor therapy for inoperable areas of the brain chronic intraparenchymal drug delivery
AU - Carson, B. S.
AU - Wu, Q.
AU - Tyler, B.
AU - Sukay, L.
AU - Raychaudhuri, R.
AU - DiMeco, F.
AU - Clatterbuck, R. E.
AU - Olivi, A.
AU - Guarnieri, M.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
KW - Brainstem tumors
KW - Carboplatin
KW - CNS cancer
KW - Intracranial drug delivery
KW - Intraparenchymal therapy
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U2 - 10.1023/A:1020626419269
DO - 10.1023/A:1020626419269
M3 - Article
C2 - 12635662
AN - SCOPUS:0036842689
VL - 60
SP - 151
EP - 158
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -