Résumé
L’incidence de l’adénocarcinome pancréatique a doublé chez l’homme et triplé chez la femme en 30 ans. La majorité des cas étant d’emblée métastatiques, son pronostic est sombre à court terme. ...Concernant la prise en charge des patients métastatiques, une chimiothérapie seule ou en association est la seule option. Tout l’enjeu de la prise en charge consiste à évaluer les patients afin de leur proposer un traitement optimal, en considérant leur tolérance attendue. La gemcitabine, traitement de référence pendant de nombreuses années, a progressivement laissé place au Folfirinox pour les patients ayant un OMS de 0 ou 1. Un des enjeux de la prise en charge est de savoir décider entre Folfirinox et nab-paclitaxel plus gemcitabine en première ligne de traitement en fonction de l’état général. La deuxième ligne métastatique n’est quant à elle pas encore bien établie, mais l’association nab-paclitaxel plus gemcitabine est très encourageante après Folfirinox. Les thérapies ciblées ne sont efficaces pour le moment qu’avec l’erlotinib et pour une contribution modeste. L’arrivée des immunothérapies concentre désormais tous les espoirs au sein d’études de phase I ou II avec le nivolumab par exemple.
Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility ...and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil.
Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts.
A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively.
Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.
Classical capacitance studies have revealed that the first layer of water present at an aqueous metal–electrolyte interface has a dielectric constant less than 1/10th of that of bulk water. Modern ...theory indicates that the barrier for electron transfer will decrease substantially in this layer; yet, this important prediction has not been tested experimentally. Here, we report the interfacial electron transfer kinetics for molecules positioned at variable distances within the electric double layer of a transparent conductive oxide as a function of the Gibbs free energy change. The data indicate that the solvent reorganization is indeed near zero and increases to bulk values only when the molecules are positioned greater than 15 Å from the conductive electrode. Consistent with this conclusion, lateral intermolecular electron transfer, parallel to a semiconducting oxide electrode, was shown to be more rapid when the molecules were within the electric double layer. The results provide much needed feedback for theoretical studies and also indicate a huge kinetic advantage for aqueous electron transfer and redox catalysis that takes place proximate to a solid interface.
A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of ...metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients.
Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit.
A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P<0.001; C6/C8, P=0.009) and satisfactory to patients (C6/C8, P=0.003) than FOLFOX-6. At the final visit, XELOX patients spent fewer days on hospital visits (3.3 vs 5.3 days, P=0.045) and lost fewer hours of work/daily activities (10.2 vs 37.1 h lost, P=0.007).
XELOX has a similar QoL profile, but seemed to be more convenient in terms of administration at certain time points and reduced time lost for work or other activities compared with FOLFOX-6.
To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients.
Two hundred thirteen patients (aged 18 to 75 years) ...with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function.
Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses CRs and 28 partial responses PRs; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern.
CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.
Breakup of an electrified viscous compound jet, surrounded by a dielectric gas, is investigated theoretically. The fluids are considered to be electrolytes and the core fluid viscosity is assumed to ...be much larger than that of the annular fluid. Axisymmetric configurations are considered with the three fluids bound by a cylindrical electrode that is held at a constant voltage potential. The model equations are investigated asymptotically in the long-wave limit, yielding two cases corresponding to a negligible surface charge with electrokinetic effects and a leaky dielectric model. A linear stability analysis for both cases is performed and the electrical effects are found to have a stabilizing effect, which is consistent with previous investigations of single electrified jet breakup at small wavenumbers. The one-dimensional equations are also solved numerically. The electric field is found to cause satellite formation in the core fluid, which does not occur in the purely hydrodynamic case, with the satellite size increasing with the strength of the electric field.
Electron-impact Excitation of Fe i Conroy, Andrew T.; Ballance, Connor P.; Ramsbottom, Catherine A. ...
The Astrophysical journal,
10/2020, Letnik:
902, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
The Fe
i
spectra emitted by astrophysical sources contain information on plasma parameters such as chemical abundances and magnetic fields. However, to determine these parameters requires ...detailed plasma modeling, which in turn needs accurate atomic data for processes such as radiative decay and electron-impact excitation in Fe
i
. A lack of fine-structure resolved collision strengths for transitions in Fe
i
is addressed in this paper with the presentation of data obtained from a Dirac
R
-matrix calculation. The suitability of our choice of target description is shown, with our energies generally within 7% of literature values. Various
A
-values are compared with other theoretical and experimental results, and the quality of the collision strengths produced in this work demonstrated. A comparison of 300- and 1000-level close-coupling expansions is made, the latter shown to eliminate pseudoresonances in the collision strengths at electron energies between 0.5 and 1.0 Ry. Maxwell-averaged effective collision strengths are presented, and the convergence of our data is shown in the temperature range 1000–100,000 K.
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