Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD genedeleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 × 10 10 to 2 × 10 13 particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dosedependent transient transaminitis were the most common

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Objective This randomized trial addressed risks and benefits of staying on antipsychotic polypharmacy versus switching to monotherapy. Method Adult outpatients with schizophrenia taking two antipsychotics (127 participants across 19 sites) were randomly assigned to Stay on Polypharmacy or Switch to Monotherapy by discontinuing one antipsychotic. The trial lasted for 6 months, with a 6-month naturalistic follow-up. Kaplan-Meier and Cox regression analyses examined time to discontinuation of assigned antipsychotic treatment, and random regression models examined additional outcomes through time. Results Individuals assigned to Switch to Monotherapy had shorter times to all-cause treatment discontinuation than those assigned to Stay (p <.05). By month 6, 86% (n=48) of those assigned to Stay on Polypharmacy were still taking both medications whereas 69% (n=40) of those assigned to Switch to Monotherapy were still taking that monotherapy. Most monotherapy discontinuations entailed returning to the original polypharmacy. Groups did not differ with respect to psychiatric symptomatology or hospitalizations. The monotherapy group lost weight whereas the polypharmacy group gained weight. Conclusions Discontinuing one of two antipsychotics was followed by treatment discontinuation more often and more quickly than when both antipsychotics were continued. However, two thirds of participants successfully switched, groups did not differ with respect to symptom control, and switching to monotherapy resulted in weight loss. This supports the reasonableness of prescribing guidelines encouraging trials of antipsychotic monotherapy for individuals receiving antipsychotic polypharmacy, with the caveat that individuals should be free to return to polypharmacy if an adequate trial on antipsychotic monotherapy proves unsatisfactory.

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The combination of CI-994 at a dose of 4 mg/m2 administered orally for 7 consecutive days can be safely coadministered with paclitaxel at a dose of 225 mg/m2 and carboplatin at an AUC of 6 on day 1 of a 21-day cycle. Evidence of antitumor activity is suggested and may correlate with histone modulation.

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SynopsisMany structural brain abnormalities have been described in schizophrenia, consistent with a neurodevelopmental model for this disease. We report here a study of the cavum septum pellucidum (CSP) in schizophrenia compared to control groups, as well as the clinical correlates of this congenital anomaly in schizophrenia. We conducted a magnetic resonance imaging (MRI) study to compare rates of CSP in schizophrenia (N = 67) v. psychiatric controls (bipolar and schizoaffective, N = 60) and healthy controls (N = 37). Of the controls 18·9 %, and of all psychotic subjects 18·1 % had a CSP of any size and there was no difference in the frequency of large CSP among the groups. Males had higher rates of CSP than females (25% v. 9·7%, P = 0·01) in all groups. Schizophrenics had higher CSP rates than affective patients (25%, v. 10%, P = 0·02). No clinical difference was found between schizophrenics with or without CSP.