Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit.

A Closed Loop Brain-machine Interface for Epilepsy Control Using Dorsal Column Electrical Stimulation

Although electrical neurostimulation has been proposed as an alternative treatment for drug-resistant cases of epilepsy, current procedures such as deep brain stimulation, vagus, and trigeminal nerve stimulation are effective only in a fraction of the patients. Here we demonstrate a closed loop brain-machine interface that delivers electrical stimulation to the dorsal column (DCS) of the spinal cord to suppress epileptic seizures. Rats were implanted with cortical recording microelectrodes and spinal cord stimulating electrodes, and then injected with pentylenetetrazole to induce seizures. Seizures were detected in real time from cortical local field potentials, after which DCS was applied. This method decreased seizure episode frequency by 44% and seizure duration by 38%. We argue that the therapeutic effect of DCS is related to modulation of cortical theta waves, and propose that this closed-loop interface has the potential to become an effective and semi-invasive treatment for refractory epilepsy and other neurological disorders.