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

To perform in 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 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.

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.

Hemispheric blood-flow estimation allowed us to escalate the dose of intra-arterial carboplatin to twice what was previously considered safe. Responses compared favorably to previous studies. Further studies are needed to determine if this method will provide improved and durable responses.