Background There are few treatment options for patients with leptomeningeal metastases (LM). Methods We report a case series of patients with breast cancer and LM treated with intra‐CSF topotecan (TOPO). Outcome was assessed by clinical exam and MRI at baseline, at end of induction (4‐5 weeks), then every 3 months; CSF cytology was determined at baseline and with each treatment. Results Thirty‐one women [median age, 58 (37‐81); median KPS 60 (40‐100)] received treatment. At baseline, 68% had positive CSF cytology, and 90%, leptomeningeal enhancement on MRI. 84% of patients also received focal RT (not during TOPO) and 77% received concomitant systemic hormonal or chemotherapy. Median number of TOPO treatments was 14.5 (range, 3‐71); median duration of treatment, 11 weeks (1‐176); and median OS, 6.9 months (range, 0.9‐48.8). Patients remaining progression‐free during 4‐6 weeks of induction (81%) had a median OS of 11.5 months (range, 1.8‐48.8). Overall neurologic PFS at 6, 12, and 24 months was 39%, 26%, and 6%, respectively. Clearing of CSF malignant cells for >3 consecutive samples occurred in 10/21 (48%) patients with positive CSF cytology at baseline, remaining clear for a median duration of 15.9 months (range, 1.4‐34.5). Grade 3 adverse events included headache or vomiting (3pts), T2 hyperintensity surrounding the ventricular catheter (2 pts), and meningitis (2 pts). Conclusions Intra‐CSF TOPO, with focal RT as needed for symptomatic areas of enhancement produced durable clearing of CSF malignant cells in 48% of patients positive at baseline, with promising median PFS and OS.

PURPOSE:To evaluate the pharmacokinetics and efficacy of imatinib in patients with recurrent oligodendroglial tumors. METHODS:Patients with progressive WHO grade II-III recurrent tumors after prior RT and chemotherapy were eligible. A phase I dose-escalation study was conducted for patients on enzyme-inducing anticonvulsants (EIAC). A phase II study for non-EIAC patients utilized a fixed dose of 600mg/D. Primary efficacy endpoint was 6-month progression-free survival (PFS6). A 2stage design was utilized, with 90% power to detect PFS6 increase from 25% to 45%. RESULTS:In the Phase I, maximum tolerated dose was not reached at 1200 mg/D. For phase II patients, overall PFS6 was 33% and median PFS 4.0 months (95% CI, 2.1, 5.7). Median overall survival (OS) was longer in imatinib-treated patients compared with controls (16.6 vs. 8.0 months; HR=0.64, 95% CI, 0.41,1.0, p=0.049), and longer in patients with 1p/19q-codeleted tumors (19.2 vs. 6.2 months, HR =0.43, 95% CI, 0.21,0.89, p=0.019). Confirmed response rate was 3.9% (PR=1; REGR=1), with stable disease observed in 52.9%. At 600 mg/D, mean steady-state imatinib plasma concentration was 2513 ng/ml (95% CI, 1831,3195). Grade 3-4 adverse events (hematologic, fatigue, GI, hypophosphatemia, or hemorrhage) occurred in 61%. CONCLUSIONS:Although adequate plasma levels were achieved, the observed PFS6 of 33% did not reach our pre-defined threshold for success. Although OS was longer in imatinib-treated

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Previous investigations have shown blacks to have a significantly lower resting heart rate (HR) compared with whites. Our purpose was to determine if this difference exists during submaximal exercise and to compare other cardiovascular responses during submaximal exercise in black and white males. Sixteen black and 16 white males matched on age, body surface area, and maximal O2 consumption exercised at 0, 50, and 100 W on a cycle ergometer. HR, O2 consumption, and cardiac output via CO2 rebreathing were measured at rest and at each work rate. Stroke volume was then calculated. O2 consumption was not significantly different between blacks and whites at rest or at work rates of 0, 50, or 100 W. Cardiac output increased from rest with 0, 50, and 100 W work for both blacks and whites (6.1 to 13.0, 14.4, and 16.9 l/min and 5.7 to 12.2, 14.3, and 16.3 l/min, respectively). The differences in cardiac output between blacks and whites at rest and all work rates were not statistically significant. At rest and work rates of 0, 50, and 100 W, HR was significantly lower in blacks compared with whites (71, 99, 108, and 119 beats/min vs. 80, 107, 114, and 127 beats/min, respectively). The lower HR in blacks compared with whites was accompanied by a trend toward a higher stroke volume at rest and work rates of 0, 50, and 100 W (85.2, 130.3, 134.7, and 142.9 ml vs. 72.5, 114.9, 126.4, and 127.4 ml, respectively). No differences in resting blood pressures were found.(ABSTRACT TRUNCATED AT 250 WORDS)

e13020 Background: Seizures are common in patients with glioma. Phenytoin, traditionally used for these patients, can be associated with intolerable side effects and potentially alters the metabolism of chemotherapeutic agents. Levetiracetam has more favorable pharmacokinetics facilitating ease of use with fewer side effects and is nonenzyme inducing. We compare seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy. Methods: Retrospective analysis of consecutive patients with glioma. Subjects had at least one clinical seizure and had to be followed for 6 months. Seizure outcomes and side effects were compared between cohorts treated with phenytoin or levetiracetam. Seizure outcomes were measured by time to second seizure and seizure frequency. Results: 76 patients (34 female) with pathologically proven glioma and seizures were identified, 25 treated with phenytoin and 51 with levetiracetam. 64% had grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p = 0.584), second seizure rates (p = 0.462), and average seizures per month (p = 0.776). When adjusting for age, gender, type of seizure, type of glioma, and dosage using univariate and multivariate models there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values >0.05). The incidence of side effects in the levetiracetam group was 5.9% versus 20% in the phenytoin group (p = 0.106). Additionally, 36.0% of the patients in the phenytoin group had dose adjustments not related to breakthrough seizures compared to only 9.8% in the levetiracetam group (p = 0.010). Conclusions: In this study, glioma patients treated with levetiracetam had similar seizure control as patients treated with phenytoin. Patients treated with levetiracetam experienced fewer side effects and required fewer non seizure related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma. No significant financial relationships to disclose.

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PURPOSE: This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of highgrade gliomas (HGGs). PATIENTS AND METHODS: A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizure attacks during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (,1 month), and follow-up (,3 months) MRI. RESULTS: After a mean follow-up of 21.9 months (range, 0.1 -88.3), seizure attacks developed in 127 patients (31%). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65%) and the follow-up MRI confirmed progression in 79 patients (62%). However, other 4 patients (3%) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24%); however, 13 patients (10%) revealed eventual progression. In the patients with a seizure, absence of preoperative seizure (p ¼ 0.003), , 95% tumor resection (p ¼ 0.001), and pre-ictal Karnofski Performance Scale score ≤ 70 (p ¼ 0.025) were significantly associated with disease progression. CONCLUSION: During the management of HGG, 31% of patients experienced seizures; of these patients, 72% harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.

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