375 research outputs found
A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma
We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m−2 on day 1; capecitabine 850 mg m−2 12-hourly on days 1–9. Level 2: as level 1 but capecitabine 1000 mg m−2. Level 3: as level 2 but irinotecan 180 mg m−2. Level 4: as level 3 but capecitabine 1250 mg m−2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3–4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16–52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study
Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer
BACKGROUND: The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR) has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD) of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT), the safety profile of this way of administration. METHODS: Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period. RESULTS: All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS). Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m(2 )met protocol-specified DLT criteria (fatigue grade 4). However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m(2)). The dose of 2,750 mg/m(2 )is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer. CONCLUSION: High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies
Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA
Events with a (2+1) jet topology in deep-inelastic scattering at HERA are
studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet
events has been determined with the modified JADE jet algorithm as a function
of the jet resolution parameter and is compared with the predictions of Monte
Carlo models. In addition, the event rate is corrected for both hadronization
and detector effects and is compared with next-to-leading order QCD
calculations. A value of the strong coupling constant of alpha_s(M_Z^2)=
0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is
extracted. The systematic error includes uncertainties in the calorimeter
energy calibration, in the description of the data by current Monte Carlo
models, and in the knowledge of the parton densities. The theoretical error is
dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.
Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA
The multiplicity structure of the hadronic system X produced in
deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic
system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY
vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant
mass M_X of the system X. Results are presented on multiplicity distributions
and multiplicity moments, rapidity spectra and forward-backward correlations in
the centre-of-mass system of X. The data are compared to results in e+e-
annihilation, fixed-target lepton-nucleon collisions, hadro-produced
diffractive final states and to non-diffractive hadron-hadron collisions. The
comparison suggests a production mechanism of virtual photon dissociation which
involves a mixture of partonic states and a significant gluon content. The data
are well described by a model, based on a QCD-Regge analysis of the diffractive
structure function, which assumes a large hard gluonic component of the
colourless exchange at low Q^2. A model with soft colour interactions is also
successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first
submission - omitted bibliograph
Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant
Jet event rates in deep inelastic ep scattering at HERA are investigated
applying the modified JADE jet algorithm. The analysis uses data taken with the
H1 detector in 1994 and 1995. The data are corrected for detector and
hadronization effects and then compared with perturbative QCD predictions using
next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2)
is determined evaluating the jet event rates. Values of alpha_S(Q^2) are
extracted in four different bins of the negative squared momentum
transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the
renormalization group equation to these several alpha_S(Q^2) values results in
alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys.
J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4
Measurements of Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Measurements of transverse energy flow are presented for neutral current
deep-inelastic scattering events produced in positron-proton collisions at
HERA. The kinematic range covers squared momentum transfers Q^2 from 3.2 to
2,200 GeV^2, the Bjorken scaling variable x from 8.10^{-5} to 0.11 and the
hadronic mass W from 66 to 233 GeV. The transverse energy flow is measured in
the hadronic centre of mass frame and is studied as a function of Q^2, x, W and
pseudorapidity. A comparison is made with QCD based models. The behaviour of
the mean transverse energy in the central pseudorapidity region and an interval
corresponding to the photon fragmentation region are analysed as a function of
Q^2 and W.Comment: 26 pages, 8 figures, submitted to Eur. Phys.
Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA
An investigation of the hadronic final state in diffractive and
non--diffractive deep--inelastic electron--proton scattering at HERA is
presented, where diffractive data are selected experimentally by demanding a
large gap in pseudo --rapidity around the proton remnant direction. The
transverse energy flow in the hadronic final state is evaluated using a set of
estimators which quantify topological properties. Using available Monte Carlo
QCD calculations, it is demonstrated that the final state in diffractive DIS
exhibits the features expected if the interaction is interpreted as the
scattering of an electron off a current quark with associated effects of
perturbative QCD. A model in which deep--inelastic diffraction is taken to be
the exchange of a pomeron with partonic structure is found to reproduce the
measurements well. Models for deep--inelastic scattering, in which a
sizeable diffractive contribution is present because of non--perturbative
effects in the production of the hadronic final state, reproduce the general
tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil
Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA
Deep--inelastic scattering events with a leading baryon have been detected by
the H1 experiment at HERA using a forward proton spectrometer and a forward
neutron calorimeter. Semi--inclusive cross sections have been measured in the
kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T
<= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV,
or a neutron with energy E' >= 160 GeV. The measurements are used to test
production models and factorization hypotheses. A Regge model of leading baryon
production which consists of pion, pomeron and secondary reggeon exchanges
gives an acceptable description of both semi-inclusive cross sections in the
region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading
neutron data are used to estimate for the first time the structure function of
the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.
A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer
The triple drug combination consisting of irinotecan, oxaliplatin and 5-fluorouracil (FOLFOXIRI) has demonstrated higher activity and efficacy compared to the doublet FOLFIRI. 5-Fluorouracil could be substituted in FOLFOXIRI regimen by capecitabine, an oral fluoropyrimidine with similar efficacy. Recently, a dose-finding trial has demonstrated the feasibility of the combination of irinotecan, oxaliplatin and capecitabine (XELOXIRI) and established their recommended doses. The aim of this study was to evaluate the activity of XELOXIRI. A total of 36 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg m−2 and oxaliplatin 85 mg m−2 on day 1 plus capecitabine 2000 mg m−2 per day orally in two doses from day 1 to day 7, every 2 weeks. Grade 3–4 toxicities were infrequent, expect for neutropenia and diarrhoea, which were each observed in 30% of patients. Two complete and twenty-two partial responses were obtained, corresponding to an overall response rate of 67% (95% CI 51.4–82%). After a median follow-up of 17.7 months, the median progression-free and overall survival were 10.1 and 17.9 months, respectively
Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy
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