Novello S.,University of Turin |
Scagliotti G.V.,University of Turin |
Sydorenko O.,Zaporizhzhya State Medical University |
Vynnychenko I.,Sumy State University |
And 6 more authors.
Journal of Thoracic Oncology | Year: 2014
Introduction: The phase 3 MONET1 study evaluated motesanib (a small-molecule inhibitor of vascular endothelial growth factor receptors) plus carboplatin/paclitaxel versus placebo plus carboplatin/ paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC). Treatment and enrollment of patients with squamous histology were permanently discontinued following higher early mortality and gross hemoptysis in those with squamous NSCLC who received motesanib. Enrollment of patients with nonsquamous histology was temporarily halted, but resumed following a protocol amendment (Scagliotti et al. J Clin Oncol. 2012;30:2829-2836). Herein, we report data from the squamous cohort. Methods: Patients with stage IIIB/IV or recurrent squamous NSCLC (without prior systemic therapy for advanced disease) received up to six 3-week cycles of chemotherapy (carboplatin, area under the curve 6 mg/L•min/paclitaxel, 200 mg2) and were randomized 1:1 to receive motesanib 125 mg (Arm A) or placebo (Arm B) once daily. The primary end point was overall survival. Results: Three-hundred and sixty patients with squamous NSCLC were randomized (Arm A, n = 182; Arm B, n = 178) between July 2007 and November 2008. Twenty-three patients (13%) in Arm A and 10 (6%) in Arm B had fatal adverse events within the first 60 days of treatment. Among these, six patients in Arm A, but none in Arm B, had fatal bleeding events. At final analysis, serious adverse events had occurred in 47% of patients in Arm A and 29% of patients in Arm B. Median overall survival was similar in Arms A and B (11.1 versus 10.7 months). Conclusions: Motesanib plus carboplatin/paclitaxel had unacceptable toxicity compared with carboplatin/paclitaxel alone in patients with advanced squamous NSCLC. Copyright © 2014 by the International Association for the Study of Lung.
Lezhenko G.,Zaporizhzhya State Medical University
Georgian medical news | Year: 2013
The purpose of this investigation is to determine the role of osteopontin and adiponectin in the formation of arterial hypertension in adolescents with obesity. 67 adolescents with obesity have been examined. Two groups were composed taking into account the state of arterial pressure. The first group included adolescents with obesity and arterial hypertension, the second group - adolescents with obesity and without arterial hypertension. Arterial pressure was measured and serum content of osteopontin, insulin, C-peptid and adiponectin in blood has been determined. The result of the investigation has revealed that in adolescents without arterial pressure the growth of insulin and C-peptid in the serum of blood has been observed; in patients with obesity and arterial hypertension the increase of content of osteopontin and hypoadiponectinemia has been occurred. The revealed changes indicated about the pathogenic role of osteopontin and adiponectin in the formation of arterial hypertension in adolescents with obesity.
Scagliotti G.V.,University of Turin |
Vynnychenko I.,Sumy State University |
Park K.,Sungkyunkwan University |
Ichinose Y.,National Kyushu Cancer Center |
And 14 more authors.
Journal of Clinical Oncology | Year: 2012
Purpose: We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/ paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non-small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma. Patients and Methods: Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m2) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS. Results: A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment. Conclusion: Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset. © 2012 by American Society of Clinical Oncology.
Hauser R.A.,University of South Florida |
Olanow C.W.,Mount Sinai School of Medicine |
Kieburtz K.D.,University of Rochester |
Pourcher E.,Laval University |
And 8 more authors.
The Lancet Neurology | Year: 2014
Background: Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in patients with Parkinson's disease who have motor fluctuations on levodopa. Methods: We did an international, multicentre, phase 2b, randomised, double-blind, placebo-controlled, parallel-group, dose-finding clinical trial of tozadenant in levodopa-treated patients with Parkinson's disease who had motor fluctuations (at least 2·5 h off-time per day). Eligible patients were randomly assigned via a computer-generated randomisation schedule to receive tozadenant 60, 120, 180, or 240 mg or matching placebo twice daily for 12 weeks. All study management, site personnel, and patients were masked to treatment assignment. The primary outcome was change from baseline to week 12 in hours per day spent in the off-state (assessed from Parkinson's disease diaries completed by patients). This study is registered at ClinicalTrials.gov, number NCT01283594. Findings: Of 420 randomised patients (mean age 63·3 [SD 8·3] years; mean duration of Parkinson's disease 8·7 [4·7] years), 403 provided post-baseline diary data and 337 completed study treatment. Compared with placebo, mean daily off-time was significantly reduced in the combined tozadenant 120 mg twice-daily and 180 mg twice-daily group (-1·1 h, 95% CI -1·8 to -0·5; p=0·0006), the tozadenant 120 mg twice-daily group (-1·1 h, -1·8 to -0·4; p=0.0039), and the tozadenant 180 mg twice-daily group (-1·2 h, -1·9 to -0·4; p=0·0039). The most common adverse events in these groups were dyskinesia (seven [8%] of 84 patients in the placebo group, 13 [16%] of 82 in the 120 mg twice-daily group, and 17 [20%] of 85 in the 180 mg twice-daily group), nausea (three [4%], 9 [11%], and ten [12%]), and dizziness (one [1%], four [5%], and 11 [13%]). Tozadenant 60 mg twice daily was not associated with a significant reduction in off-time, and tozadenant 240 mg twice daily was associated with an increased rate of discontinuation because of adverse events (17 [20%] of 84 patients). Interpretation: Tozadenant at 120 or 180 mg twice daily was generally well tolerated and was effective at reducing off-time. Further investigation of tozadenant treatment in phase 3 trials is warranted. Funding: Biotie Therapies. © 2014 Elsevier Ltd.
Antypenko O.M.,Zaporizhzhya State Medical University |
Kovalenko S.I.,Zaporizhzhya State Medical University |
Karpenko O.V.,Enamine Ltd
Synthetic Communications | Year: 2016
A series of tetrazolo[1,5-c]quinazolines were synthesized by [4 + 1]-cyclocondensation of 4-hydrazinoquinazolines with sodium nitrite with good yields. Peculiarities of this reaction were discussed, namely, the influence of halogen on the reaction yield. Hydrolytic cleavage of tetrazolo[1,5-c]quinozoline cycle was studied in order to obtain 2-(1H-tetrazolo-5-yl)anilines. The structures of the compounds were elucidated by 1H NMR, 13C NMR, infrared, mass spectrometry, and elemental analysis. 2016 Copyright © Taylor & Francis Group, LLC