Intra-arterial carboplatin chemotherapy for brain tumors: A dose escalation study based on cerebral blood flow

Abstract

Purpose. To perform an intra-arterial dose escalation studyof carboplatin based on hemispheric blood-flow estimation inpatients with recurrent malignant glioma. The primary purposewas to determine the maximally tolerated intra-arterial dose.Methods and patients. Methods included: 1) selective intra-arterialdelivery performed with modern microcatheters, 2) pulsatile infusion,and 3) dosage based on local cerebral blood-flowestimation (middle cerebral artery 60%, anterior cerebral artery20%, posterior cerebral artery 15%, and anterior choroidalartery 5% of the hemispheric blood-flow). The deliverieswere performed above the ophthalmic artery in theanterior circulation, or above the anterior inferior cerebellararteries in the posterior circulation. The doses wereescalated from 200 mg/hemisphere at 50 mg increments.Twenty-one patients were studied (14 with glioblastoma multiforme,five anaplastic astrocytoma, one aggressive low-grade glioma, onemetastasis). Patients had recurrent glioma limited to onehemisphere and Karnofsky score of 50 or greater.Concomitant therapies were allowed. Results. Carboplatin was escalatedto a dose of 1400 mg/hemisphere. One patienthad a permanent neuromotor decline. The predominant toxicitywas hematopoietic. The median time to tumor progressionwas 22 weeks, median survival 39 weeks, andthe response rate 70% (50% SD and 20%PR) of 19 patients. Conclusions. Hemispheric blood-flow estimationallowed us to escalate the dose of intra-arterialcarboplatin to twice what was previously considered safe.Responses compared favorably to previous studies. Further studiesare needed to determine if this method willprovide improved and durable responses.