A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig

Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. VI. Variability of NGC 3783 from ground-based data

The Seyfert 1 galaxy NGC 3783 was intensely monitored between 1991 December and 1992 August. We present the results from the ground-based observations in the optical and near-IR, which complement the data-set from the IUE, discussed elsewhere. Spectroscopic and photometric data from many observatories were combined in order to obtain well sampled light curves of the continuum and of H-Beta. During the campaign the source varied significantly. The light curves of the optical continuum and of H-Beta are similar to those obtained with the IUE. The near-IR flux did not vary significantly except for an increase at the end of the campaign. The optical continuum and the flux of H-Beta lag the UV continuum by 1 day or less and by 8 days respectively. These results confirm that the continuum variations are simultaneous or have a very small lag across the entire UV-optical range, and that the lines of NGC 3783 respond to ionizing continuum variations with less delay than those of NGC 5548. As in NGC 5548, the lag of H-Beta is greater than those of the high ionization lines.Comment: 34 pages in LaTeX, 7 postscript figures available on request from [email protected] or 37907::stirpe, BAP#10-1993-035-OA

Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Multiwavelength observations of short time-scale variability in NGC 4151. I. Ultraviolet observations

We present the results of an intensive ultraviolet monitoring campaign on the Seyfert 1 galaxy NGC 4151, as part of an effort to study its short time-scale variability over a broad range in wavelength. The nucleus of NGC 4151 was observed continuously with the {\it International Ultraviolet Explorer} (IUE) for 9.3 days, yielding a pair of LWP and SWP spectra every $\sim$70 minutes, and during four-hour periods for 4 days prior to and 5 days after the continuous monitoring period. The sampling frequency of the observations is an order of magnitude higher than that of any previous UV monitoring campaign on a Seyfert galaxy. The continuum fluxes in bands from 1275 \AA\ to 2688 \AA\ went through four significant and well-defined ``events'' of duration 2 -- 3 days during the continuous monitoring period. We find that the amplitudes of the continuum variations decrease with increasing wavelength, which extends a general trend for this and other Seyfert galaxies to smaller time scales (i.e., a few days). The continuum variations in all of the UV bands are {\it simultaneous} to within an accuracy of about 0.15 days, providing a strict constraint on continuum models. The emission-line light curves show only one major event during the continuous monitoring (a slow rise followed by a shallow dip), and do not correlate well with continuum light curves over the (short) duration of the campaign, because the time scale for continuum variations is apparently smaller than the response times of the emission lines.Comment: 39 pages, LaTeX, including 7 PostScript figures; To appear in the ApJ (October 20, 1996) Vol. 47

Multiwavelength observations of short time-scale variability in NGC 4151. IV. Analysis of multiwavelength continuum variability

This paper combines data from the three preceding papers in order to analyze the multi-waveband variability and spectral energy distribution of the Seyfert~1 galaxy NGC~4151 during the December 1993 monitoring campaign. The source, which was near its peak historical brightness, showed strong, correlated variability at X-ray, ultraviolet, and optical wavelengths. The strongest variations were seen in medium energy ($\sim$1.5~keV) X-rays, with a normalized variability amplitude (NVA) of 24\%. Weaker (NVA = 6\%) variations (uncorrelated with those at lower energies) were seen at soft $\gamma$-ray energies of $\sim$100~keV. No significant variability was seen in softer (0.1--1~keV) X-ray bands. In the ultraviolet/optical regime, the NVA decreased from 9\% to 1\% as the wavelength increased from 1275~\AA\ to 6900~\AA. These data do not probe extreme ultraviolet (1200~\AA\ to 0.1~keV) or hard X-ray (2--50~keV) variability. The phase differences between variations in different bands were consistent with zero lag, with upper limits of \ls0.15~day between 1275~\AA\ and the other ultraviolet bands, \ls0.3~day between 1275~\AA\ and 1.5~keV, and \ls1~day between 1275~\AA\ and 5125~\AA. These tight limits represent more than an order of magnitude improvement over those determined in previous multi-waveband AGN monitoring campaigns. The ultraviolet fluctuation power spectra showed no evidence for periodicity, but were instead well-fitted with a very steep, red power-law ($a = -2.5$). If photons emitted at a ``primary" waveband are absorbed by nearby material and ``reprocessed" to produce emission at a secondary waveband, causality arguments require that variations in the secondary band follow those in the primary band. The tight interband correlation and limits on the ultraviolet andComment: 35 pages, LaTeX (including aaspp4), including 7 PostScript figures; To appear in the ApJ (October 20, 1996) Vol. 47

Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. 5: Variability of the ultraviolet continuum and emission lines of NGC 3783

We report on the results of intensive ultraviolet spectral monitoring of the Seyfert 1 galaxy NGC 3783. The nucleus of NGC 3783 was observed with the International Ultraviolet Explorer satellite on a regular basis for a total of 7 months, once every 4 days for the first 172 days and once every other day for the final 50 days. Significant variability was observed in both continuum and emission-line fluxes. The light curves for the continuum fluxes exhibited two well-defined local minima or 'dips,' the first lasting is less than or approximately 20 days and the second is less than or approximately 4 days, with additional episodes of relatively rapid flickering of approximately the same amplitude. As in the case of NGC 5548 (the only other Seyfert galaxy that has been the subject of such an intensive, sustained monitoring effort), the largest continuum variations were seen at the shortest wavelengths, so that the continuum became 'harder' when brighter. The variations in the continuum occurred simultaneously at all wavelengths (delta(t) is less than 2 days). Generally, the amplitude of variability of the emission lines was lower than (or comparable to) that of the continuum. Apart from Mg II (which varied little) and N V (which is relatively weak and badly blended with Ly(alpha), the light curves of the emission lines are very similar to the continuum light curves, in each case with a small systematic delay or 'lag.' As for NGC 5548, the highest ionization lines seem to respond with shorter lags than the lower ionization lines. The lags found for NGC 3783 are considerably shorter than those obtained for NGC 5548, with values of (formally) approximately 0 days for He II + O III), and approximately 4 days for Ly(alpha) and C IV. The data further suggest lags of approximately 4 days for Si IV + O IV) and 8-30 days for Si III + C III). Mg II lagged the 1460 A continuum by approximately 9 days, although this result depends on the method of measuring the line flux and may in fact be due to variability of the underlying Fe II lines. Correlation analysis further shows that the power density spectrum contains substantial unresolved power over timescales of is less than or approximately 2 days, and that the character of the continuum variability may change with time

Obesity indexes and total mortality among elderly subjects at high cardiovascular risk: The PREDIMED study

Different indexes of regional adiposity have been proposed for identifying persons at higher risk of death. Studies specifically assessing these indexes in large cohorts are scarce. It would also be interesting to know whether a dietary intervention may counterbalance the adverse effects of adiposity on mortality. METHODS: We assessed the association of four different anthropometric indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index (BMI) and height) with all-cause mortality in 7447 participants at high cardiovascular risk from the PREDIMED trial. Forty three percent of them were men (55 to 80 years) and 57% were women (60 to 80 years). All of them were initially free of cardiovascular disease. The recruitment took place in 11 recruiting centers between 2003 and 2009. RESULTS: After adjusting for age, sex, smoking, diabetes, hypertension, intervention group, family history of coronary heart disease, and leisure-time physical activity, WC and WHtR were found to be directly associated with a higher mortality after 4.8 years median follow-up. The multivariable-adjusted HRs for mortality of WHtR (cut-off points: 0.60, 0.65, 0.70) were 1.02 (0.78-1.34), 1.30 (0.97-1.75) and 1.55 (1.06-2.26). When we used WC (cut-off points: 100, 105 and 110 cm), the multivariable adjusted Hazard Ratios (HRs) for mortality were 1.18 (0.88-1.59), 1.02 (0.74-1.41) and 1.57 (1.19-2.08). In all analyses, BMI exhibited weaker associations with mortality than WC or WHtR. The direct association between WHtR and overall mortality was consistent within each of the three intervention arms of the trial. CONCLUSIONS: Our study adds further support to a stronger association of abdominal obesity than BMI with total mortality among elderly subjects at high risk of cardiovascular disease. We did not find evidence to support that the PREDIMED intervention was able to counterbalance the harmful effects of increased adiposity on total mortality. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN35739639

Multiwavelength Observations of Short-Timescale Variability in NGC 4151. I. Ultraviolet Observations

We present the results of an intensive ultraviolet monitoring campaign on the Seyfert I galaxy NGC 4151, as part of an effort to study its short-timescale variability over a broad range in wavelength. The nucleus of NGC 4151 was observed continuously With the International Ultraviolet Explorer for 9.3 days, yielding a pair of LWP and SWP spectra every ~70 minutes, and during 4 hr periods for 4 days Prior to and 5 days after the continuous-monitoring period. The sampling frequency of the observations is an order of magnitude higher than that of any previous UV monitoring campaign on a Seyfert galaxy. The continuum fluxes in bands from 1275 to 2688 A went through four significant and well-defined events of duration 2-3 days during the continuous-monitoring period. We find that the amplitudes of the continuum variations decrease with increasing wavelength, which extends a general trend for this and other Seyfert galaxies to smaller timescales (i.e., a few days). The continuum variations in all the UV bands are simultaneous to within an accuracy of ~0.15 days, providing a strict constraint on continuum models. The emission-line light curves show only one major event during the continuous monitoring (a slow rise followed by a shallow dip) and do not correlate well with continuum light curves over the short duration of the campaign, because the timescale for continuum variations is apparently smaller than the response times of the emission lines.Astronom