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[Background] To assess the efficacy and safety of a metronomic schedule of oral vinorelbine (mVNR) in advanced non-small-cell lung cancer (NSCLC) in patients unfit for platinum-based combination chemotherapy., [Patients and methods] This was a multicenter, prospective, randomized, open-label phase II study in treatment-naive patients with TNM stage IIIB/IV NSCLC. Patients received mVNR at a fixed dose of 50 mg × 3 or standard schedule 60-80 mg/m2 weekly until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) without grade 4 toxicity (G4PFS; NCI-CTC v4). Main secondary objectives were safety, disease control rate (DCR) without grade 4 toxicity (G4DCR), DCR, PFS, overall survival (OS) and quality of life (QoL)., [Results] A total of 167 patients were included, 83 and 84 patients in the mVNR and standard arms, respectively. The median G4PFS was 4.0 months [95% confidence interval (CI): 2.6-4.3] and 2.2 months (95% CI: 1.5-2.9), hazard ration (HR) = 0.63 (95% CI: 0.45-0.88), P = 0.0068 in favor of metronomic arm; G4DCR was 45.8% and 26.8% in the mVNR and standard arms, respectively. Grade 3-4 treatment-related adverse events were less frequent in the mVNR arm (25.3% versus 54.4%) mainly owing to a reduction in all grades (15.7% versus 51.9%) and grade 3-4 neutropenia (10.8% versus 42%). PFS was 4.3 (95% CI: 3.3-5.1) and 3.9 months (95% CI: 2.8-5.2) in mVNR and standard arms, respectively. No difference in median OS was observed. QoL was comparable between arms., [Conclusions] Metronomic oral vinorelbine significantly prolonged median G4PFS in advanced NSCLC patients unfit for platinum combinations as first-line treatment. It was associated with a clear reduction in toxicity and may be considered as an important option in this challenging population., Pierre Fabre Médicament was the Sponsor of the study. The study was funded by Pierre Fabre Médicament. Conduct of the study: Pierre Fabre Médicament with the support of Clinipace clinical research organization (CRO) for the monitoring, of C-Med (CRO) for the data management and statistical analyses.

Background Tempo-Lung trial randomly assessed the role of metronomic oral vinorelbine (OV) vs standard weekly oral vinorelbine in advanced NSCLC patients (pts) unfit to platinum doublets. Little data are available on treatment options after first-line in platinum-unfit pts. Methods Advanced NSCLC pts unfit to receive platinum doublets (Creatinine clearance G2; any medical condition impairing platinum treatment according to physician’s opinion) were randomized to arm A (metronomic): OV 50mg x3/week (wk) or arm B (standard): OV 60 mg/m²/wk cycle 1, then 80 mg/m²/wk. Primary endpoint was progression free-survival without grade 4 toxicity (PFSG4) and secondary efficacy and safety end-point, quality of life (QoL). Data on treatment after failure of first-line vinorelbine were collected. Results Intention-to-treat population included 165 (arm A 83 - arm B 82) pts. Baseline characteristics were well balanced between both arms. Mean dose intensity by cycle: 73.56 mg/m²/week (arm A), 55.85 mgm²/week (arm B). Median PFSG4 significantly differ in favor of metronomic arm [95%CI]: 4.0 [2.6-4.3] vs 2.2 [1.5-2.9] months (p = 0.0068), HR [95%CI] = 0.63 [0.45-0.88]. Overall treatment related adverse events (61.4% vs 84%): haematological toxicities (27.7% vs 55.6%), G3/4 neutropenia (11% vs 42%), febrile neutropenia (3.6% vs 6.2%) and G3/4 asthenia (4.8% vs 8.6%) were reduced with metronomic OV. It was observed that 40% of patients (subset) had second line treatment: immunotherapy, chemotherapy, protein kinase inhibitor, radiotherapy. No difference was found for changes in EORTC QoL scores. Secondary endpoints will be presented. Conclusions Metronomic OV could be a suitable option for advanced NSCLC pts unfit to receive platinum doublets. Less toxicity was observed in metronomic arm. QoL scores were similar in both arms. A subset of platinum unfit patients could receive second-line treatment mainly consisting on immunotherapy, chemotherapy. Clinical trial identification 2014-003859-61. Legal entity responsible for the study IRPF, Pierre Fabre Medicament. Funding Pierre Fabre Medicament. Disclosure A. Camerini: Speaker Bureau / Expert testimony, expert testimony: Pierre Fabre; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Pierre Fabre. A. Morabito: Speaker Bureau / Expert testimony, speaker bureau: Pfizer; Speaker Bureau / Expert testimony, speaker bureau: BMS; Speaker Bureau / Expert testimony, speaker bureau: MSD; Speaker Bureau / Expert testimony, speaker bureau: Roche; Speaker Bureau / Expert testimony, speaker bureau: AstraZeneca; Speaker Bureau / Expert testimony, speaker bureau: Boehringer Ingelheim. F. Grossi: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Honoraria (self): Eli Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pierre Fabre; Honoraria (self): BMS; Honoraria (self): Novartis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): MSD. R. Ramlau: Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Boehringer Ingelheim. T-E. Ciuleanu: Advisory / Consultancy: Astellas; Advisory / Consultancy: Janssen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: A et D Pharma; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Boehringer Ingelheim; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Ipsen. G.L. Ceresoli: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy: Boehringer Ingelheim. J. Bosch-Barrera: Honoraria (self): Pierre Fabre; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): BMS; Advisory / Consultancy: Boehringer Ingelheim. P. Landreau: Full / Part-time employment: Pierre Fabre. S. Gautier: Full / Part-time employment: Pierre Fabre. C. Ta Thanh Minh: Full / Part-time employment: Pierre Fabre. All other authors have declared no conflicts of interest.

Background Metronomic chemotherapy (CT) is a therapeutic strategy based on a regular, short interval, fixed-dose schedule developed to improve disease control and reduce toxicity. Metronomic oral vinorelbine (m-OV) showed promising results. The trial randomly compared single agent m-OV vs OV standard schedule as first-line treatment in advanced NSCLC patients (pts) unfit for platinum-based CT (P-CT). Methods CT naive pts with advanced NSCLC unfit for P-CT (Creatinine clearance G2; medical conditions impairing P-CT according to physician’s opinion) were 1:1 randomly allocated to arm A: m-OV 50mg x3/week (wk) or arm B: OV 60 mg/m²/wk cycle 1, then 80 mg/m²/wk. Primary objective: progression-free survival without grade 4 toxicity (G4PFS). Secondary objectives: disease control rate (DCR), PFS, overall survival (OS), safety, quality of life. Stratification factors: stage (IIIB vs IV), age ( 70 yrs) and ECOG PS (0-1 vs 2). Results Intention-to-treat (ITT) population included 165 pts: 83 pts (A) / 82 (B). Pt characteristics were well balanced (A vs B): mean age 76.1 vs 75.9 yrs; ECOG PS 0-1: 66% vs 62%; Stage IV: 87% vs 94% pts. Median relative dose intensity was 85% vs 69%. Primary endpoint was reached (A vs B) with median G4PFS [95%CI]: 4.0 [2.6-4.3] vs 2.2 [1.5-2.9] months (mo) (p = 0.0068), HR [95%CI] = 0.63 [0.45-0.88]. Secondary efficacy end-points were as follows (A vs B): DCR 63.9% vs 63.4%; median PFS 4.3 vs 3.9 mo; median OS: 7.1 vs 7.6 mo. Treatment related AEs (r-AEs) A vs B were: all grade 61.4% vs 84%; total hematological AEs: 27.7% vs 55.6%. Most common (≥ 5%) grade 3-4 r-AEs (A vs B) were: febrile neutropenia 3.6% vs 6.2%; neutropenia 11% vs 52%; asthenia 4.8% vs 8.6%. One grade 5 AE occurred in each arm (febrile neutropenia, neutropenic sepsis). Conclusions Positive results of first randomized prospective trial: m-OV significantly improved G4PFS as first-line CT in advanced unfit NSCLC pts, with reduced toxicity. Treatment efficacy was similar in both arms. m-OV is a suitable, safe option for first-line therapy of NSCLC pts unfit to P-CT. Clinical trial identification EudraCT: 2014-003859-61. Legal entity responsible for the study Institut de Recherche Pierre Fabre- Pierre Fabre Medicament. Funding Institut de Recherche Pierre Fabre- Pierre Fabre Medicament. Disclosure A. Morabito: Speaker Bureau / Expert testimony, Speaker Bureau: Pfizer; Speaker Bureau / Expert testimony, Speaker Bureau: BMS; Speaker Bureau / Expert testimony, Speaker Bureau: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Speaker Bureau: MSD; Speaker Bureau / Expert testimony, Speaker Bureau: Roche; Speaker Bureau / Expert testimony, Speaker Bureau: AstraZeneca. F. Grossi: Honoraria (self): Ely Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pierre Fabre; Honoraria (self): BMS; Honoraria (self): Amgen; Honoraria (self): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD; Advisory / Consultancy: Ely Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Honoraria (self): Celgene. R. Ramlau: Advisory / Consultancy: Roche; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. T. Ciuleanu: Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Advisory / Consultancy, Travel / Accommodation / Expenses: A et D Pharma; Travel / Accommodation / Expenses: Ipsen. G.L. Ceresoli: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy: Boehringer Ingelheim. J. Bosch Barrera: Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Honoraria (self): BMS; Advisory / Consultancy: Boehringer Ingelheim. P. Landreau: Full / Part-time employment: Pierre Fabre. S. Gautier: Full / Part-time employment: Pierre Fabre. C. Ta Thanh Minh: Full / Part-time employment: Pierre Fabre. A. Camerini: Speaker Bureau / Expert testimony, expert testimony: Pierre Fabre; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Titanium oxide TiO2 has found extensive use in a great variety of applications among which electrode materials for dye-sensitized solar cells. The polymorphs of TiO2, rutile, anatase and brookite exhibit specific physical properties, band gap, electronic surface states. For many applications the size of particles was an important parameter because it determines the surface to volume ratio, which greatly influences many properties. TiO2 anatase was the most used phase for photovoltaic applications and brookite seems potentially interesting. Nanometric particles of the three polymorphs were synthesized in aqueous medium in order to compare the electronic properties of these materials for photovoltaic devices. No significant difference was observed between the phases by cyclic voltammetry. The surface and consequently the electrode preparation seemed to be the main parameter. The measurement of double layer capacitance has shown the film activation initially insulating and strong frequency dependence. After dye sensitization, it has been observed that at low I2 concentration in solution (with a fixed concentration of I−), the open circuit voltage (Voc) was independent of this concentration while above a certain threshold for I2, Voc decreased logarithmically with the iodine concentration.