Direct constraint on the distance of y2 Velorum from AMBER/VLTI observations

In this work, we present the first AMBER observations, of the Wolf-Rayet and O (WR+O) star binary system y2 Velorum. The AMBER instrument was used with the telescopes UT2, UT3, and UT4 on baselines ranging from 46m to 85m. It delivered spectrally dispersed visibilities, as well as differential and closure phases, with a resolution R = 1500 in the spectral band 1.95-2.17 micron. We interpret these data in the context of a binary system with unresolved components, neglecting in a first approximation the wind-wind collision zone flux contribution. We show that the AMBER observables result primarily from the contribution of the individual components of the WR+O binary system. We discuss several interpretations of the residuals, and speculate on the detection of an additional continuum component, originating from the free-free emission associated with the wind-wind collision zone (WWCZ), and contributing at most to the observed K-band flux at the 5% level. The expected absolute separation and position angle at the time of observations were 5.1±0.9mas and 66±15° respectively. However, we infer a separation of 3.62+0.11-0.30 mas and a position angle of 73+9-11°. Our analysis thus implies that the binary system lies at a distance of 368+38-13 pc, in agreement with recent spectrophotometric estimates, but significantly larger than the Hipparcos value of 258+41-31 pc

Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument

We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K band observations were performed with the AMBER instrument of the ESO Very Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines from 42 to 89m. The aim of this work is to study the wavelength dependence of Eta Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The medium spectral resolution observations (R=1,500) were performed in the wavelength range around both the HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high spectral resolution observations (R=12,000) only in the Br gamma line region. In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range 28-89m) was measured for Eta Car's optically thick wind region. If we fit Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17 micron continuum, the HeI, and the Br gamma emission lines, respectively. In the continuum near the Br gamma line, an elongation along a position angle of 120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by van Boekel et al. (2003). We compare the measured visibilities with predictions of the radiative transfer model of Hillier et al. (2001), finding good agreement. Furthermore, we discuss the detectability of the hypothetical hot binary companion. For the interpretation of the non-zero differential and closure phases measured within the Br gamma line, we present a simple geometric model of an inclined, latitude-dependent wind zone. Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m−2) and cyclophosphamide (2 g m−2) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m−2 and thiotepa 200 mg m−2. At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m−2 cyclophosphamide and 400 mg m−2 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p

Factors of interrupting chemotherapy in patients with Advanced Non-Small-Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure. Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status (PS) > 2 and an LDH > 600 UI/L were independent prognostic factors. In this prospective study, which included 45 patients, we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified.</p> <p>Findings</p> <p>Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre (Centre Léon Bérard). Clinical assessment and blood parameters were recorded and considered. Patient prognostic factors for overall survival (OS) with a 0.05-significance level in univariate analysis were entered in a multivariate Cox model for further analysis.</p> <p>Patients' median age was 58.5 years (range: 37 - 76). Sixty two percent of the patients were PS = 0 or 1. After inclusion, nine patients received second-line (22.5%), and two received third-line chemotherapy (5%). Univariate analysis showed that the factors associated with reduced OS were: PS > 2, weight loss >10%, more than one line of chemotherapy treatment and abnormal blood parameters (hemoglobin (Hb), platelet and neutrophils counts). Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival. According to the presence of none (33%), 1 (37%) and 2 (30%) prognostic factors, median OS were 12, 5 and 2 months respectively.</p> <p>Conclusion</p> <p>From this prospective study, both PS and anemia were found as independent determinants of survival, we found that both PS and anemia were independent determinants of survival. The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line.</p

Tolerability of gefitinib in patients receiving treatment in everyday clinical practice

Gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has recently been approved in several countries for use in advanced or metastatic non-small-cell lung cancer (NSCLC). In contrast to chemotherapies, which are generally used at or near their maximum-tolerated dose (MTD), gefitinib is used at an optimal biological dose (250 mg day−1), which is substantially below its MTD, minimising the risk of adverse events without compromising efficacy. Tolerability data from the compassionate use of gefitinib in the ‘Iressa’ Expanded Access Programme support the favourable safety profile of the agent reported in Phase I and II trials. In both settings, the majority of adverse drug reactions were mild/moderate and consisted mainly of grade 1/2 diarrhoea and skin rash. Although skin rash has been suggested to predict response to gefitinib, available data do not support this hypothesis. Overall, these tolerability data demonstrate that gefitinib has a relatively benign side-effect profile and is a well-tolerated treatment option for patients with previously treated NCSLC, who currently have few alternatives

Constraining the wind launching region in Herbig Ae stars: AMBER/VLTI spectroscopy of HD 104237

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. We investigate the origin of the Brγ emission of the Herbig Ae star HD 104237 on Astronomical Unit (AU) scales. Methods. Using AMBER/VLTI at a spectral resolution R = 1500 we spatially resolve the emission in both the Brγ line and the adjacent continuum. Results. The visibility does not vary between the continuum and the Brγ line, even though the line is strongly detected in the spectrum, with a peak intensity 35% above the continuum. This demonstrates that the line and continuum emission have similar size scales. We assume that the K-band continuum excess originates in a “puffed-up” inner rim of the circumstellar disk, and discuss the likely origin of Brγ. Conclusions. We conclude that this emission most likely arises from a compact disk wind, launched from a region 0.2–0.5 AU from the star, with a spatial extent similar to that of the near infrared continuum emission region, i.e., very close to the inner rim location.This work has been partly supported by the MIUR COFIN grant 2003/027003-001 and 025227/2004 to the INAFOsservatorio Astrofisico di Arcetri. This project has benefited from funding from the French Centre National de la Recherche Scientifique (CNRS) through the Institut National des Sciences de l’Univers (INSU) and its Programmes Nationaux (ASHRA, PNPS). The authors from the French laboratories would like to thank the successive directors of the INSU/CNRS directors. C. Gil work was supported in part by the Fundac¸˜ao para a Ciˆencia e a Tecnologia through project POCTI/CTE-AST/55691/2004 from POCTI,with funds from the European program FEDER

Interferometric data reduction with AMBER/VLTI. Principle, estimators, and illustration

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. In this paper, we present an innovative data reduction method for single-mode interferometry. It has been specifically developed for the AMBER instrument, the three-beam combiner of the Very Large Telescope Interferometer, but it can be derived for any single-mode interferometer. Methods. The algorithm is based on a direct modelling of the fringes in the detector plane. As such, it requires a preliminary calibration of the instrument in order to obtain the calibration matrix that builds the linear relationship between the interferogram and the interferometric observable, which is the complex visibility. Once the calibration procedure has been performed, the signal processing appears to be a classical least-square determination of a linear inverse problem. From the estimated complex visibility, we derive the squared visibility, the closure phase, and the spectral differential phase. Results. The data reduction procedures have been gathered into the so-called amdlib software, now available for the community, and are presented in this paper. Furthermore, each step in this original algorithm is illustrated and discussed from various on-sky observations conducted with the VLTI, with a focus on the control of the data quality and the effective execution of the data reduction procedures. We point out the present limited performances of the instrument due to VLTI instrumental vibrations which are difficult to calibrate.The AMBER project4 was founded by the French Centre National de la Recherche Scientifique (CNRS), the Max Planck Institute für Radioastronomie (MPIfR) in Bonn, the Osservatorio Astrofisico di Arcetri (OAA) in Firenze, the French Region “Provence Alpes Côte D’Azur” and the European Southern Observatory (ESO). The CNRS funding has been made through the Institut National des Sciences de l’Univers (INSU) and its Programmes Nationaux (ASHRA, PNPS, PNP). The OAA co-authors acknowledge partial support from MIUR grants to the Arcetri Observatory: A LBT interferometric arm, and analysis of VLTI interferometric data and From Stars to Planets: accretion, disk evolution and planet formation and from INAF grants to the Arcetri Observatory Stellar and Extragalactic Astrophysics with Optical Interferometry. C. Gil work was supported in part by the Fundação para a Ciência e a Tecnologia through project POCTI/CTE-AST/55691/2004 from POCTI, with funds from the European program FEDER