INTRAARTERIAL CARBOPLATIN CHEMOTHERAPY FOR BRAIN-TUMORS - A DOSE-ESCALATION STUDY BASED ON CEREBRAL BLOOD-FLOW

Purpose. To perform an intra-arterial dose escalation study of carbopl atin based on hemispheric blood-flow estimation in patients with recur rent malignant glioma. The primary purpose was to determine the maxima lly tolerated intra-arterial dose. Methods and patients. Methods inclu ded: 1) selective intra-arterial delivery performed with modern microc atheters, 2) pulsatile infusion, and 3) dosage based on local cerebral blood-flow estimation (middle cerebral artery 60%, anterior cerebral artery 20%, posterior cerebral artery 15%, and anterior choroidal arte ry 5% of the hemispheric blood-flow). The deliveries were performed ab ove the ophthalmic artery in the anterior circulation, or above the an terior inferior cerebellar arteries in the posterior circulation. The doses were escalated from 200 mg/hemisphere at 50 mg increments. Twent y-one patients were studied (14 with glioblastoma multiforme, five ana plastic astrocytoma, one aggressive low-grade glioma, one metastasis). Patients had recurrent glioma limited to one hemisphere and Karnofsky score of 50 or greater. Concomitant therapies were allowed. Results. Carboplatin was escalated to a dose of 1400 mg/hemisphere. One patient had a permanent neuromotor decline. The predominant toxicity was hema topoietic. The median time to tumor progression was 22 weeks, median s urvival 39 weeks, and the response rate 70% (50% SD and 20% PR) of 19 patients. Conclusions. Hemispheric blood-flow estimation allowed us to escalate the dose of intra-arterial carboplatin to twice what was pre viously considered safe. Responses compared favor ably to previous stu dies. Further studies are needed to determine if this method will prov ide improved and durable responses.