Meningiomas represent 18-20% of all intracranial tumors and have a 10-year recurrence rate of 20-50%, despite aggressive surgery and irradiation. In addition, many tumors are not amenable to surgery due to their deep location or proximity to delicate structures. Chemotherapy is being explored as another potential treatment option for unresectable or refractory meningiomas. Hydroxyurea is an agent that inhibits ribonucleotide reductase and can induce apoptosis in meningioma cell cultures and animal models. We have placed 17 patients with unresectable or residual meningioma on hydroxyurea chemotherapy (20 mg/kg/d orally). The mean age of our cohort was 57.2 years; 13 patients were female. Eleven patients had actively growing tumors or neurological progression at the onset of chemotherapy. Sixteen patients were evaluable for response. Fourteen of the 16 patients (88%) responded with stable disease ranging from 20 to 144+ weeks (median 80 weeks; 10 patients still accruing time). Three of the responders progressed after 20, 36, and 56 weeks, respectively. Two patients had progressive disease after 10 weeks. Toxicity was hematologic in most patients; leukopenia was most common. Nine patients (53%) required dosage reductions (250-500 mg/d) secondary to hematologic toxicity. Hydroxyurea appears to have modest activity against meningiomas and should be considered in patients with unresectable tumors or large residual tumors following surgical resection.
Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer and often respond poorly to treatment. Median survival is only 16-24 weeks after conventional radiation therapy. Regional intra-arterial (IA) administration of chemotherapy results in increased tumor uptake of drug and may improve response rates and survival. Twenty-seven patients with MBT who had received prior irradiation were treated with IA carboplatin (200 mg/m2/d) and intravenous (i.v.) etoposide (100 mg/m2/d) for 2 days every 3-4 weeks. Eighteen patients (67%) had received prior systemic chemotherapy for their primary tumor. Patients ranged in age from 19 to 68 years (mean 48.1). Thirteen of 24 evaluable patients had objective responses (54.2%). There were 6 complete responses (25%), 6 partial responses (25%), 1 minor response (4.2%), 7 stable disease (32%), and 5 progressive disease (20.8%). Some patients with multifocal tumors had a mixture of responses. The median time to progression was 16.0 weeks overall and 30.0 weeks in responders (range 6-118 weeks). Overall median survival from the time of protocol initiation was 20.0 weeks. In six responders, death occurred due to systemic illness unrelated to MBT progression. Therapy was well tolerated, with predominantly hematologic toxicity. Angiographic complications were rare. Although these are preliminary results, IA carboplatin and IV etoposide is safe and well tolerated, appears to be active against brain metastases, and warrants further study.
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