99 research outputs found
Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials
The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area
The aim of this study was to evaluate the risk of thrombo-embolic events (TEE) in patients with germ-cell tumours (GCT) who receive cisplatin-based chemotherapy, to compare this risk to that of a matched control group of non-GCT cancer patients, and to identify risk factors of TEE. The rate of TEE during the 6 months following the initiation of chemotherapy was assessed in 100 consecutive patients with GCT and in 100 controls with various neoplasms who were matched on sex and age, and who received first-line cisplatin-based chemotherapy during the same period of time at Institut Gustave Roussy, Villejuif, France. Data were subsequently tested on a validation group of 77 GCT patients treated in Lyon, France. A total of 19 patients (19%) (95% confidence interval (CI): 13–28) and six patients (6%) (95% CI: 3–13) had a TEE in the GCT group and the non-GCT control group, respectively (relative risk (RR): 3.4; P<0.01). Three patients from the GCT group died of pulmonary embolism. In multivariate analysis, two factors had independent predictive value for TEE: a high body surface area (>1.9 m2) (RR: 5 (1.8–13.9)) and an elevated serum lactate dehydrogenase (LDH) (RR: 6.4 (2.3–18.2)). Patients with no risk factor (n=26) and those with at least one risk factor (n=71) had a probability of having a TEE of 4% (95% CI: 1–19) and 26% (95% CI: 17–37), respectively. In the GCT validation set, 10 (13%) patients had a TEE; patients with no risk factor and those with at least one risk factor had a probability of having a TEE of 0 and 17% (95% CI: 10–29), respectively. Patients with GCT are at a higher risk for TEE than patients with non-GCT cancer while on cisplatin-based chemotherapy. This risk can be accurately predicted by serum LDH and body surface area. This predictive index may help to study prospectively the impact of thromboprophylaxis in GCT patients
Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial
Background
Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane.
Methods
In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436.
Findings
Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment.
Interpretation
Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations
Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population
Exploitation domestique de l'Ă©nergie solaire. Influence du climat
A critical study, valid for Belgium and the East of France, is made of the incidence of climatic conditions on the domestic use of solar energy. Using energy recordings of global radiation analysed over a period of about twelve years, we observe a remarkable constancy in the global daily average per month. However, the daily global during any one month is of an essentially fluctuating size with the differences able to exceed five times the weakest value. The day's energy quality may be estimated by basing ourselves on the global between 11 and 12 o'clock (TSV). The possible performances of a plane collector using the greenhouse effect first in thermostatics and then in thermokinetics are next examined. Finally, we evaluate the needs necessary to a home's heating and consider the perspectives opened in this field by the use of solar radiation.On fait une étude critique, valable pour la Belgique et l'Est de la France, de l'incidence des conditions climatiques sur l'utilisation domestique de l'énergie solaire. A partir des enregistrements énergétiques du rayonnement global analysé sur une douzaine d'années on observe une constance remarquable du global moyen journalier par mois. Par contre le global journalier durant un mois quelconque est une grandeur essentiellement fluctuante avec des écarts pouvant dépasser plus de 5 fois la valeur la plus faible. La qualité énergétique du jour peut être appréciée en se fixant sur le global entre 11 h et 12 h (TSV). On examine ensuite les performances possibles d'un capteur plan utilisant l'effet de serre en thermostatique puis en thermocinétique. On évalue enfin les besoins nécessaires au chauffage d'une habitation et on fait le bilan des perspectives ouvertes dans ce domaine par l'emploi du rayonnement solaire
Ultrastructural study of the interactions and fusion of ram spermatozoa with zona-free hamster oocytes
International audienc
Exploitation domestique de l'Ă©nergie solaire. Influence du climat
On fait une étude critique, valable pour la Belgique et l'Est de la France, de l'incidence des conditions climatiques sur l'utilisation domestique de l'énergie solaire. A partir des enregistrements énergétiques du rayonnement global analysé sur une douzaine d'années on observe une constance remarquable du global moyen journalier par mois. Par contre le global journalier durant un mois quelconque est une grandeur essentiellement fluctuante avec des écarts pouvant dépasser plus de 5 fois la valeur la plus faible. La qualité énergétique du jour peut être appréciée en se fixant sur le global entre 11 h et 12 h (TSV). On examine ensuite les performances possibles d'un capteur plan utilisant l'effet de serre en thermostatique puis en thermocinétique. On évalue enfin les besoins nécessaires au chauffage d'une habitation et on fait le bilan des perspectives ouvertes dans ce domaine par l'emploi du rayonnement solaire
- …