Diffuse leptomeningeal involvement by a ganglioglioma in a child. Case report.

Gangliogliomas are tumors composed of neuronal and glial elements that typically grow slowly by expansion only. This report describes a 20-month-old girl with a ganglioglioma that extensively involved the subarachnoid space; microscopic foci of tumor were found in the brain and spinal cord. Despite chemotherapy and radiation therapy, the child died 5 months after diagnosis. Molecular genetic analysis showed loss of chromosome 17p DNA sequences in the tumor tissue.     

Temozolomide in the treatment of recurrent malignant glioma

BACKGROUND: Options for chemotherapy at the time of recurrence in patients with malignant glioma are limited. The authors describe the efficacy and safety results of their institution's open-label, compassionate-use protocol of temozolomide for patients with recurrent malignant glioma. METHODS: Patients with recurrent malignant glioma at any time during recurrence were treated with oral temozolomide at a dose of 150 mg/m2 per day on a 5-day schedule every 28 days. If this dose was tolerated, then escalation to 200 mg/m2 was allowed. Clinical evaluations and assessments of tumor response were performed every 2 months. All patients or their surrogates signed approved Institutional Review Board consent forms. RESULTS: Among 213 patients who were treated, 33% had Grade 3 tumors, and 67% had Grade 4 tumors. The overall objective response rate was 16% in both of these patient groups; and an additional 51% and 30% of patients with Grade 3 and Grade 4 tumors, respectively, had stable disease as their best response. The 6-month progression-free survival rates were 41% and 18% for patients with Grade 3 and Grade 4 tumors, respectively. The median survival was 49 weeks for patients with Grade 3 tumors and 32 weeks for patients with Grade 4 tumors. The major toxicity was hematologic toxicity. In multivariate analysis, the Karnofsky performance score was a significant predictor of survival for patients with Grade 4 tumors. CONCLUSIONS: Temozolomide was well tolerated in patients with recurrent malignant glioma and had modest efficacy, even at the time of multiple recurrences.     

Safety, Tolerability, and Tumor Response of IL4-Pseudomonas Exotoxin (NBI-3001) in Patients with Recurrent Malignant Glioma

Purpose: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. Patients and methods: A total of 31 patients with histologically verified supratentorial grades 3 and 4 astrocytoma were studied. Of these, 25 patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma. Patients were over 18 years of age and had Karnofsky performance scores 60. Patients were assigned to one of four dose groups in a dose-escalation fashion: 6µg/ml×40ml,9µg/ml×40ml,15µg/ml×40ml, or 9µug/ml×100ml of NBI-3001 administered via convection-enhanced delivery intratumorally using stereotactically placed catheters. Patients were followed with serial MRI scans and clinical assessments every four weeks for the first 16 weeks and then every eight weeks until week 26. Results: No drug-related systemic toxicity, as evident by lack of hematological or serum chemical changes, was apparent in any patients; treatment-related adverse effects were limited to the central nervous system. No deaths were attributable to treatment. Drug-related grade 3 or 4 toxicity was seen in 39% of patients in all dose groups and 22% of patients at the maximum tolerated dose of 6µug/ml×40ml. The overall median survival was 8.2 months with a median survival of 5.8 months for the GBM patients. Six-month survival was 52% and 48%, respectively. Gadolinium-enhanced magnetic resonance imaging of the brain showed areas of decreased signal intensity within the tumor consistent with tumor necrosis following treatment in many patients. Conclusions: NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma.     

A randomized,double-blind,placebo-controlled,phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma

RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP). Adults with recurrent glioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or placebo. Radiation therapy had failed in all patients, and they may have received prior chemotherapy. Carboplatin (dosed to achieve an area under the curve of 5 mg/ml x time for patients who had received prior chemotherapy, or 7 mg/ml x time for those who had not) was given intravenously every 4 weeks, followed by intravenous infusion of either RMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychological assessments, functional independence, and quality of life assessments were analyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60 in the placebo and carboplatin group. Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0 weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin group. Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differences were noted for time to worsening of neuropsychological assessments, functional independence, or quality of life assessments. The use of RMP-7 had no effect on the pharmacokinetics or toxicity of carboplatin. At the dose and schedule used in this trial, RMP-7 did not improve the efficacy of carboplatin. Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses of RMP-7 may be required to increase carboplatin delivery to tumor.     

A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American Brain Tumor Consortium report

BACKGROUND: The primary objective of the current study was to determine the response rate of paclitaxel in patients with recurrent malignant glioma by using different doses dependent on the concomitant use of anticonvulsants. Secondary objectives were to determine the time period to treatment failure, to evaluate toxicities, and to obtain pharmacokinetic data. METHODS: Adult patients who had recurrent malignant glioma were treated with paclitaxel. Patients were treated at different doses depending on the concomitant use of anticonvulsants known to induce the p450 hepatic enzyme system. Patients on such agents were treated at a dose of 330 mg/m2, whereas those not on these anticonvulsants were treated at a dose of 210 mg/m2. Tumor response was assessed at 6-week intervals. Treatment was continued until documented tumor progression or unacceptable toxicity occurred, or a total of 12 paclitaxel infusions was completed. RESULTS: From January 1997 to June 1997, 23 patients were treated with paclitaxel. Four patients were ineligible for the current study. Of the 19 eligible patients, there were no responses seen. Four (21%) had stabilization of disease. Median time to treatment failure was 1 month (95% confidence interval [CI], 1-2 mos) and median survival was 7 months (95% CI, 6-10 mos). Three patients were removed from the current study because they had toxicity. Pharmacokinetic studies demonstrated that drug levels and clearance values were consistent with previously reported findings. CONCLUSION: Even though higher doses were administered to patients who had recurrent malignant glioma and who were on concomitant anticonvulsants, there were no objective responses to paclitaxel. Time to tumor progression was 1 month. Further testing of paclitaxel at this dose schedule does not appear to be warranted in this patient population.