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

Purpose. To perform an intra-arterial dose escalation study of carboplatin based on hemispheric blood-flow estimation in patients with recurrent malignant glioma. The primary purpose was to determine the maximally tolerated intra-arterial dose. Methods and patients. Methods included: 1) selective intra-arterial delivery performed with modern microcatheters, 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 artery 5% of the hemispheric blood-flow). The deliveries were performed above the ophthalmic artery in the anterior circulation, or above the anterior inferior cerebellar arteries in the posterior circulation. The doses were escalated 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, 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 hematopoietic. The median time to tumor progression was 22 weeks, median survival 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 previously considered safe. Responses compared favor ably to previous studies. Further studies are needed to determine if this method will provide improved and durable responses.