Anaplastic oligodendrogliomas are chemosensitive brain cancers. Patients with these tumors respond predictably, durably, and often completely to PCV, and many tolerate a dose-escalated formulation. Cooperative group and randomized trials will be necessary to explore fully the role of chemotherapy in the treatment of aggressive oligodendrogliomas.

Seizures are reported to occur in at least 20% of patients with metastatic or primary brain tumour. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Brain tumour patients who present with seizures are treated with anticonvulsants but these drugs are frequently used prophylactically. A generalized seizure may be lethal if it is prolonged or if the patient does not recover consciousness. [18][19][20][21][22] Seizures may cause unacceptable toxicity or interact with other drugs, such as corticosteroids [23][24][25] or chemotherapeutic agents which may compromise the patient's overall treatment. Retrospective studies of prophylactic anticonvulsants in patients with metastases have been conflicting ABSTRACT: Objective: We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. Methods: One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Results: Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥ 900 patients to have a suitably powered study. Conclusions: These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure.RÉSUMÉ: Une question importante en neuro-oncologie à la quelle il est difficile de répondre: l'utilité des anticonvulsivants prophylactique chez les patients porteurs d'une tumeur cérébrale. Objectif: Nous avons procédé à un essai thérapeutique pour déterminer si les anticonvulsivants administrés de façon préventive chez les patients porteurs d'une tumeur cérébrale, sans épisode convulsif antérieur, réduisent la fréquence des crises épileptiques. Nous avons limité le recrutement à 100 patients suite à une analyse intérimaire. Méthodes: Cent patients, atteints de tumeurs cérébrales dont le diagnostic était récent, ont reçu des anticonvulsivants (groupe AC) ou n'en ont pas reçu (groupe sans AC) dans le cadre d'un...

Purpose: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates.Experimental Design: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys.Results: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus' antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates.Conclusions: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities.

BACKGROUND: Novel therapies are needed to improve outcomes in T-cell lymphomas. The authors report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas. METHODS: Patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and untreated patients ineligible for combination chemotherapy were prescribed oral lenalidomide (25 mg daily) on Days 1 to 21 of each 28-day cycle until disease progression, death, or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The 2-stage design allows for up to 40 patients. RESULTS: At the time of this interim analysis, 24 patients were enrolled in this study, and 23 were evaluable for response. The median age was 65 years. The overall response rate was 7 (30%) of 23; all were partial responses. Two patients had stable disease for !5 cycles. Responses were seen in anaplastic, angioimmunoblastic, and peripheral Tcell unspecified histologies. Median PFS was 96 days (range, 8-696þ days). Median OS was 241 days (range, 8-696þ days). The most common grade 4 adverse event was thrombocytopenia (33%). The most common grade 3 adverse events were neutropenia (21%), febrile neutropenia (17%), and pain not otherwise specified (17%). Rash correlated with response to therapy (P ¼.003). CONCLUSIONS: In patients with recurrent and refractory T-cell lymphomas, oral lenalidomide monotherapy has clinical activity, and toxicity is consistent with the known safety profile of lenalidomide. Further study of lenalidomide in these diseases is warranted. Cancer 2010;116:4541-8.

We evaluated the accuracy of cardiac output estimations by three transthoracic echocardiographic techniques in critically ill subjects. This study was a prospective comparison study carried out in a general intensive care unit of a teaching hospital. The subjects had a broad range of diagnoses including pulmonary embolus, cardiogenic shock, septic shock, Legionnaire's disease and perioperative myocardial infarction. All patients requiring pulmonary artery catheterization underwent echocardiographic cardiac assessment with comparison of findings to those obtained by thermodilution techniques. Nineteen studies on eighteen patients were performed, with cardiac output calculated by the two-chamber Simpson's, four-chamber Simpson's, and left ventricular outflow tract (LVOT) Doppler methods. Acceptable data was obtained in those patients without mitral regurgitation. There was good correlation between the thermodilution technique and Simpson's two-chamber method (r=0.91), but less so with the Simpson's fourchamber method (r=0.77). All studies were included in the LVOT Doppler method with a good correlation (r=0.94). A plot of differences between methods using the Bland and Altman statistical method indicated that only the LVOT Doppler method demonstrated acceptable agreement with a mean of 0.2 litres/minute, standard deviation of 0.82 litres/minute and 95% limits of agreement of -1.5 to +1.9 litres/minute.We concluded that the LVOT Doppler method was the only one which demonstrated acceptable agreement between the thermodilution method and echocardiographic techniques in all critically ill patients studied.