Sunitinib is a tyrosine kinase inhibitor with direct anti-tumor and anti-angiogenesis activity targeting VEGFR 1-2, PDGFR α-β, c-kit, bFGF, (CSF-1), FLT3 and RET. The present trial examined the activity of sunitinib in 12 patients with newly diagnosed, non-resectable glioblastoma. Patients (≤75 years of age with performance status [PS] ≥2 and minimental status [MMS] ≥25) were treated post-biopsy with sunitinib 37.5 mg daily for 8 weeks pre-radiotherapy, during radiotherapy (60 Gy, 6 weeks) and post-radiotherapy until disease progression. The primary endpoints were overall response rate (ORR; RANO criteria) after 8 weeks of sunitinib and patient tolerance. Secondary endpoints were percentage of patients free of neurological deterioration pre-radiotherapy, percentage of patients completing radiotherapy, progression-free survival (PFS), overall survival (OS), and 1-year survival. A Simon 2-stage design (12 →20) based on ORR was applied to calculate the number of patients needed to detect at least 10 % response with α error of 0.05 and β error of 0.10. The trial was closed because it did not meet minimal activity criteria. ORR was 0 % with only 1/12 patients (8.3 %) achieving stable disease after sunitinib treatment. No patient showed reduction in gadolinium enhancement. The most frequent G3/4 toxicities were fatigue (24.9 %) and diarrhea (16.6 %); one patient died of a CNS hemorrhage; 10/12 patients (83.3 %) deteriorated neurologically before radiation therapy; median PFS was 7.7 weeks (95 % CI: 7.2-8.2); median OS was 12.8 weeks (95 % CI: 0.5-23.8 weeks); 1-year survival was 0 %. Sunitinib has no activity as monotherapy in glioblastoma, and further investigation of its efficacy in this setting is unwarranted.

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IntroductionNew designer benzodiazepines such as phenazepam, etizolam, diclazepam, clonazolam and flubromazolam have appeared in the recreational drug market due to that they provide an attractive alternative to prescription-only benzodiazepines as they are readily available over the Internet.ObjectiveTo describe the presence of new designer benzodiazepines in samples delivered to energy control since 2010 to 2016 in Barcelona.MethodsFrom 2010 to 2016, 24,551 samples were delivered to energy control. Among this samples 43 (0.175%) were analysed as benzodiazepines. They were analyzed by energy control, a Spanish harm reduction NGO that offers the possibility of analyzing the substances that users report. Analysis was done by gas chromatography-mass spectrometry.ResultsFrom the 43 samples analyzed as benzodiazepines, 1 (2.32%) was delivered in 2010, none in 2011, 2 (4.65%) in 2012, 2 (4.65%) in 2013, 1 (2.32%) in 2014, 15 (34.88%) in 2015 and 21 (48.83%) in 2016.DiscussionThe data shows that new designer benzodiazepines use is increasing in Barcelona, especially in the last two years. Abuse an addiction to these drugs may be a new public health problem in Barcelona. Unknown side effects may appear due to lack of information about pharmacokinetic profile of these drugs.Disclosure of interestThe authors have not supplied their declaration of competing interest.