Phase I study of intracarotid administration of carboplatin.

Fifteen patients were treated in a Phase I study of intracarotid carboplatin (200-400 mg/m2) in 5% dextrose and water infused over 15 to 30 minutes through a transfemoral catheter with a 0.2-micron inline filter. This study was done because intravenous carboplatin has less neurotoxicity than cisplatin and is active against brain tumors. Eleven men and four women ranging in age from 37 to 72 years (median, 59 years) were treated. The Eastern Cooperative Oncology Group performance status was 1 in 3, 2 in 4, and 3-4 in 8 patients. Eight patients had one to three previous chemotherapy regimens; previous radiotherapy had failed in 13 patients. The response of patients in the Phase I study follows: glioblastoma, 6 failed; not evaluated because of early death from pulmonary embolus, 1; recurrent Grade II and III glioma, 1 stable (minor response with neurologic improvement) and 2 failed; malignant oligodendroglioma, 1 failed; brain metastases from nonsmall cell lung cancer, 1 partial remission, 1 stable (minor response), and 1 failed; brain metastases from unknown primary, 1 stable (minor response with neurological improvement). Median survival was 9 weeks. Nausea was mild to moderate. One patient had granulocytopenia, and 2 had thrombocytopenia (mild). At 200 mg/m2 (2 patients), 1 had a focal seizure. At 300 mg/m2 (9 patients), 2 with abnormally small arteries had severe pain early in the treatment and posttreatment ipsilateral conjunctival edema, decreased vision, and cerebral edema (with partially reversible increased hemiparesis); 1 other had mild decrease in ipsilateral vision and 1 had transient aphasia on removal of the catheter (possibly the result of a vascular spasm).(ABSTRACT TRUNCATED AT 250 WORDS)

Association of pleomorphic xanthoastrocytoma with cortical dysplasia and neuronal tumors. A report of three cases.

BACKGROUND: Several recent publications indicate that pleomorphic xanthoastrocytoma (PXA) may occasionally express ganglionic cell differentiation, linking this type of tumor to other benign, mixed glioneuronal neoplasms. Furthermore, ganglionic tumors and less frequently some benign glial tumors in the central nervous system, could be associated with a variety of mild developmental abnormalities of the cerebral cortex that are classified under the broad term cortical dysplasia. The association of cortical dysplasia with PXA and a neuronal pattern of differentiation has not been reported previously. METHODS: The authors present clinical, radiologic, immunohistochemical, and ultrastructural findings in three patients with cortical dysplasia. The cortical dysplasia was continuous with PXA, displaying an additional component of neuronal cell differentiation. RESULTS: The ages of the patients were 23, 47, and 52 years. Resection of the tumors was predated by temporal lobe seizures by 6 years in 1 patient and by more than 30 years in the others. In all 3 cases, radiologic studies conducted 3-6 years before surgery showed either no abnormality or lesions that were initially nonprogressing. CONCLUSIONS: The longstanding clinical history of seizures and the existence of radiologically documented dormant lesions several years before tumor removal both suggest that PXA in these patients very likely developed in benign hamartomatous cortical lesions or in preexisting cortical dysplasia. The authors' findings, along with the consistent occurrence of PXA in the gray matter in the majority of the reported cases, indicate that these tumors may originate either from a subclass of astrocytes histogenetically and topographically associated with neurons or from multipotential neuroectodermal precursor cells common to neurons and astrocytes.

Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults.

Twenty patients with astrocytomas recurrent after surgery +/- radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.