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.
Recurrent and progressive non-GBM gliomas are a diverse group of brain tumors that often respond poorly to adjuvant chemotherapy treatment. Regional intra-arterial (IA) administration of chemotherapy may result in increased tumor uptake of drug, with improvement in response rates and time to progression (TTP). Twenty-five patients with recurrent or progressive non-GBM gliomas were treated with IA carboplatin (200 mg/m2/d) and intravenous (IV) etoposide (100 mg/m2/d) for 2 days every 4 weeks. Patients ranged in age from 22 to 68 years (mean 37.8). All but one patient had received standard irradiation, and eight patients had attempted prior chemotherapy. Five of 25 patients had objective responses (20%), while another 15 patients had stable disease (60%), receiving a total of 318 IA treatment procedures. There was one complete response (4.0%), three partial responses (12.0%), one minor response (4.0%), 15 stable diseases (60.0%), and five progressive diseases (20.0%). The median TTP was 24.2 weeks overall and 32 weeks in responders. Overall median survival was 34.2 weeks. Therapy was well tolerated, with mainly hematologic toxicity. Two patients had embolic complications. Although these are preliminary results, IA carboplatin and IV etoposide have modest activity against recurrent and progressive non-GBM gliomas and warrants further study.
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