Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study.

Asunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Intraventricular silicone oil.

The authors report a case in which intravitreous silicone oil migrated into the ventricles. They note that intraventricular silicone oil can be misdiagnosed as intraventricular hemorrhage and neurosurgeons should be aware of this possibility. This 58-year-old woman with a history of Type II diabetic mellitus and retinal detachment (resulting from diabetic retinopathy), which had been treated with intravitreous silicone tamponade, presented with dizziness and headache approximately 10 years after the intravitreous silicone treatment. Over the next 6 years she underwent 2 non-contrast-enhanced brain CT studies and 1 MRI study for evaluation of her symptoms. On CT scan, extension of the intraocular silicone along the optic nerve was evident. Two hyperdense nodules were observed freely floating in the right lateral and fourth ventricles, remaining in the nondependent portion of ventricles in both supine and prone positions. On T2-weighted MRI, the left orbital content and the intraventricular nodules all demonstrated chemical shift artifacts typically associated with silicone. The imaging findings were characteristic for intraventricular silicone after silicone oil tamponade. The patient's dizziness and headache were treated symptomatically and she was followed up at the outpatient department. Migration of intravitreous silicone oil into the cerebral ventricles is a rare complication. Intraventricular silicone oil can mimic intraventricular hemorrhage. Radiographically, intraventricular silicone oil can be distinguished from hemorrhage as silicone oil tends to stay in the nondependent portion of the ventricle. Chemical shift artifacts on MRI may help establishing the diagnosis of intraventricular silicone oil. Currently, there is no consensus on surgical removal of intraventricular silicone oil, and in the majority of cases reported in the literature, the patients were asymptomatic.