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1.
Water Sci Technol ; 82(11): 2513-2524, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33339804

RESUMO

Cotton cloth waste was used as a precursor to prepare activated carbon (ACCs) chemically activated with phosphoric acid. Adsorption behavior of prepared ACCs was correlated with physicochemical proprieties. The pore volume and BET surface of ACCs were determined by nitrogen adsorption isotherms and scanning electron microscopy was used to observe their surface morphologies. Fourier transform infrared (FTIR) spectroscopy analysis and pH point zero charge (pHPZC) were conducted to determine chemical properties. Under the optimal conditions: 50% impregnation ratio and thermal treatment under N2 flow at 600 °C during 60 min, the activated carbon prepared exhibits a high surface area 1,150 m2/g, 0.501 cm3/g micropore volume and an excellent adsorption performance. The adsorbed amount of clofibric acid is found to be 9.98 and 83 mg/g at, respectively, initial CA concentration of 10 and 100 mg/L at pH 3.0 and 20 °C. Diffusion and chemisorption are the steps controlling the adsorption of CA onto ACC 50% and the equilibrium data were well described by Freundlich isotherm.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Adsorção , Ácido Clofíbrico , Concentração de Íons de Hidrogênio , Cinética , Ácidos Fosfóricos , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
2.
Gynecol Oncol ; 158(3): 666-672, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32624235

RESUMO

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.


Assuntos
Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Ovarianas/terapia , Conduta Expectante , Adolescente , Adulto , Idoso , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Coriocarcinoma/cirurgia , Coriocarcinoma/terapia , Disgerminoma/tratamento farmacológico , Disgerminoma/patologia , Disgerminoma/cirurgia , Disgerminoma/terapia , Tumor do Seio Endodérmico/tratamento farmacológico , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/cirurgia , Tumor do Seio Endodérmico/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Teratoma/tratamento farmacológico , Teratoma/patologia , Teratoma/cirurgia , Teratoma/terapia , Adulto Jovem
3.
Cancer Radiother ; 24(4): 279-287, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32439358

RESUMO

PURPOSE: The present study evaluated the outcomes of concurrent weekly docetaxel and platinum-based drug doublet in association with concurrent thoracic radiotherapy (TR) in the curative treatment of stage III locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIA/B NSCLC were retrospectively included. Patients received weekly docetaxel and either cisplatin or carboplatin intravenous injections during concurrent TR (60 to 66Gy). Patients who received induction chemotherapy with the same drug doublet were also included. The endpoints were: disease control rate (DCR), overall recurrence rate, survival rates [disease-free survival (DFS) and overall survival (OS)] and toxicity. RESULTS: Eighty-nine consecutive patients treated with this association were included. Median follow-up time was 57.8 months. DCR was 76.5% at the first follow-up CT scan (6 to 12 weeks after the end of concurrent treatment). Median DFS and OS was 14.3 and 29.9 months respectively. Three-year survival was 43%. The overall recurrence rate was 65.9%. During overall treatment, grade 3 to 4 adverse events occurred in 29.2% of patients, the most common being esophagitis (12.4% of patients). Only 13.5% of patients presented with a grade 3 or higher adverse event after the end of concurrent treatment. CONCLUSIONS: Weekly docetaxel and platinum-based drug doublet combined with TR yielded promising results in stage III NSCLC, with high survival rates. The toxicity of this association is acceptable, with mainly manageable esophagitis. These findings warrant validation in a prospective study before considering this association for standard of care.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/métodos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
4.
Ann Oncol ; 31(2): 289-294, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959346

RESUMO

BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Resultado do Tratamento , Vemurafenib/uso terapêutico
5.
Lupus ; 28(5): 642-650, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30907294

RESUMO

OBJECTIVES: The aims of this study are (1) to characterize factors influencing self-management behaviors and quality of life in adolescent and young adult (AYA) patients with childhood-onset systemic lupus erythematosus (cSLE) and (2) to identify barriers and facilitators of treatment adherence via focus groups. METHODS: AYAs with cSLE ages 12-24 years and primary caregivers of the adolescents participated in this study. Recruitment occurred during pediatric rheumatology clinic visits at a Midwestern children's hospital or the hospital's cSLE active clinic registry. Information about disease severity was obtained from patient health records. Pain and fatigue questionnaires were administered. Descriptive statistics were used to analyze data. RESULTS: Thirty-one AYA patients and caregivers participated in six focus groups. Ten major themes emerged from sessions; four were expressed both by the AYA and caregiver groups: knowledge deficits about cSLE, symptoms limiting daily function, specifically mood and cognition/learning, barriers and facilitators of adherence, and worry about the future. Themes unique to AYA participants included symptoms limiting daily functioning-pain/fatigue, self-care and management, impact on personal relationships, and health care provider communication/relationship. For caregiver groups unique themes included need for school advocacy, disruption of family schedule, and sense of normalcy for their adolescent. CONCLUSION: AYAs with cSLE face a lifelong disease characterized by pervasive pain, fatigue, organ damage, isolation-social and/or physical-and psycho-socioeducational challenges. This study confirmed that continued psychosocial support, health information education, adherence interventions, and personalized treatment plans are necessary to increase self-management and autonomy in AYAs with cSLE.


Assuntos
Cuidadores/psicologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Autogestão , Adolescente , Idade de Início , Criança , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Lúpus Eritematoso Sistêmico/terapia , Masculino , Ohio , Cooperação do Paciente , Qualidade de Vida , Sistema de Registros , Inquéritos e Questionários , Adulto Jovem
6.
Rev Medisan ; 22(9)2018.
Artigo em Espanhol | CUMED | ID: cum-79338

RESUMO

RESUMEN: Se realizó una investigación descriptiva, de serie de casos, de 31 pacientes ingresados en la Unidad de Cuidados Intensivos del Hospital Provincial Docente Clinicoquirúrgico“Saturnino Lora Torres” de Santiago de Cuba, de enero de 2014 a igual mes de 2017,quienes presentaron el síndrome de insuficiencia respiratoria aguda, con vistas a describir los factores pronóstico de mortalidad por esta causa. En la serie predominaron el sexo masculino, la edad promedio de 57 años y la hipertensión arterial como enfermedad crónica asociada. La mayoría de los pacientes recibía ventilación mecánica previa al diagnóstico, en la modalidad controlada por volumen, y en un menor número se aplicaron maniobras de incorporación alveolar. La insuficiencia respiratoria moderada de causa extrapulmonar figuró en pacientes con ventilación prolongada, en tanto la complicación más frecuente fue la disfunción multiorgánica, que además resultó la principal causa de muerte. Finalmente, no se encontró relación directa entre la presencia de estos factores pronóstico de mortalidad y la probabilidad de fallecer.[AU]


Assuntos
Humanos , Insuficiência Respiratória , Prognóstico , Mortalidade , Respiração Artificial , Cuidados Críticos
7.
Nat Commun ; 8: 15228, 2017 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-28485400

RESUMO

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability.

8.
Br J Cancer ; 116(3): 303-309, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28072765

RESUMO

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.


Assuntos
Aminopiridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Morfolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Quimioterapia Adjuvante , Progressão da Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Recidiva , Resultado do Tratamento
9.
Ann Oncol ; 25(11): 2191-2196, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25210017

RESUMO

BACKGROUND: Lenalidomide has dual antiangiogenic and immunomodulatory properties and confirmed antitumor activity in hematologic malignancies. A phase II study investigating the safety and efficacy of continuous lenalidomide in recurrent ovarian cancer patients was initiated. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, with asymptomatic recurrence 6 months after prior therapy were treated with continuous oral lenalidomide (20 mg/day). The primary end point was to evaluate efficacy according to the rate of disease control at 4 months. Secondary objectives were progression-free survival (PFS) and safety. RESULTS: Most of the 45 patients enrolled and treated had serous histology (78%) and a single line of prior chemotherapy (73%). Median platinum-free interval (PFI) was 11.3 months (range 6.9-56.8). Clinical benefit at 4 months was 38% [95% confidence interval (CI) 23% to 53%]. A 59% disease control rate was reported in patients with a PFI >12 months versus 24% with PFI of 6-12 months (P = 0.023). Four patients had RECIST partial responses and 21 had stable disease. CA125 responses were reported in eight patients, including one complete response. Median PFS was 3.4 months (95% CI 2.4-4.4). Most frequent toxicity was hematologic, notably grade 3-4 neutropenia in 29% of patients, along with fatigue (69%), gastrointestinal toxicity (constipation 53%, abdominal pain 49%, diarrhea 38%, nausea/vomiting 36%) and thrombosis (11%). Eight patients withdrew due to related toxicity. CONCLUSIONS: Lenalidomide shows interesting efficacy in late recurrent ovarian cancer patients. Toxicity was mainly hematologic, gastrointestinal and venous thrombosis. Future studies will evaluate combination of lenalidomide with chemotherapy agents. CLINICALTRIALSGOV: NCT01111903.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias das Tubas Uterinas , Feminino , Humanos , Lenalidomida , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Platina/efeitos adversos , Talidomida/administração & dosagem , Talidomida/efeitos adversos
11.
Br J Cancer ; 108(9): 1771-7, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23612453

RESUMO

BACKGROUND: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. METHODS: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. RESULTS: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22-52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). CONCLUSION: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Idoso , Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Everolimo , Feminino , Humanos , Pessoa de Meia-Idade , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Taxa de Sobrevida
12.
Br J Cancer ; 107(4): 598-603, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22790797

RESUMO

BACKGROUND: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours. METHODS: Patients received intravenous aflibercept 4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination. RESULTS: During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs. CONCLUSION: Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Receptores de Fatores de Crescimento do Endotélio Vascular
13.
Ann Oncol ; 22(2): 321-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20693300

RESUMO

BACKGROUND: Very effective trastuzumab-based primary systemic therapy (PST) can be proposed for conservative surgery purpose to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HER2+BC). Long-term follow-up (LTFU) warrants further data. PATIENTS AND METHODS: LTFU of patients, with stage II/III HER2+BC, treated by trastuzumab associated with docetaxel (Taxotere(®)) and/or carboplatin used as anthracycline-free PST was studied. RESULTS: Among 135 patients, with a median follow-up of 48.3 months [95% confidence interval (CI) 45.3-52.4 months], the relapse-free survival (RFS) rate was 73.2% (95% CI 63.76% to 80.55%) while the overall survival (OS) rate was 91.87% (95% CI 84.23% to 95.90%). Adjuvant trastuzumab favorably influenced RFS in univariate analysis while the pathological nodal invasion unfavorably influenced RFS [Cox multivariate analysis (hazard ratio = 2.80, 95% CI 1.36-5.76, P = 0.0052)] and OS. Cardiac toxicity was minor (2.2% transient, reversible asymptomatic decrease in left ventricular ejection fraction). CONCLUSION: This is the first report of LTFU showing that anthracycline-free trastuzumab-based PST combined either with docetaxel and/or carboplatin can achieve, without cardiac toxicity, very competitive results in terms of pathological complete response, RFS and OS, in HER2+BC. The choice of this schedule could be proposed to patients with vascular contraindication for anthracyclines or because patient's or physician's preference for a taxane-only schedule.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Genes erbB-2 , Neoplasias da Mama/genética , Estudos de Coortes , Feminino , Seguimentos , Humanos
14.
Br J Cancer ; 103(9): 1335-42, 2010 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-20978512

RESUMO

BACKGROUND: We analysed whether the level of human epidermal growth factor receptor-2 (HER-2) amplification significantly influenced either pathological complete response (pCR) or recurrence-free survival (RFS) and overall survival (OS) after trastuzumab-based neoadjuvant therapy. METHODS: In all, 99 patients with an HER-2-amplified breast tumour treated with trastuzumab-based neoadjuvant therapy were included. Tumours were classified as low amplified (LA; 6-10 signals per nuclei) or highly amplified (HA; >10 signals). Pathological response was assessed according to Chevallier's classification (pCR was defined as grade 1 or 2). Median follow-up lasted 46 months (6-83). Cox uni- and multivariate analyses were performed. RESULTS: In all, 33 tumour samples were LA and 66 were HA. The pCR in HA tumours was significantly higher than in LA tumours (55% vs 24%, P=0.005), whereas no association was found between the pCR rate and tumour stage, grade or hormone receptor status. In multivariate analysis, the pathological nodal status (P=0.005) and adjuvant trastuzumab (P=0.037) were independently associated with RFS, whereas the level of HER-2 amplification nearly reached statistical significance (P=0.057). There was no significant difference between LA and HA tumours for OS (P=0.22, log-rank). CONCLUSION: The level of HER-2 gene amplification significantly influenced pCR but not RFS or OS in non-metastatic breast cancer treated with trastuzumab-based neoadjuvant therapy. However, RFS in patients with HA tumours tended to be shorter.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Genes erbB-2 , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Amplificação de Genes , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Indução de Remissão , Trastuzumab
15.
Ann Fr Anesth Reanim ; 29(9): 621-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20634026

RESUMO

INTRODUCTION: We determined whether the implementation of a bundle of 10 recommendations leads to the reduction of mortality in ICU patients with severe sepsis or septic shock. METHODS: All patients with severe sepsis or septic shock during two consecutive phases: a 6-month quality control period (observational) and secondly a 6-month intervention period based on the implementation of a bundle of 10 recommendations adapted from the Surviving Sepsis Campaign guidelines (initial bacteriological samples and initiating antibiotics, measurement of arterial lactate, volume expansion > or =20 ml/kg, targeted mean arterial pressure > or =65 mmHg and the assessments of central venous pressure and Scv(O2); glucose control, low doses of corticosteroids, a tidal volume < or =8 ml/kg in mechanically ventilated patients with ALI; adequate use of recombinant human activated protein C) were evaluated in 15 ICUs. The primary endpoint was the 28-day mortality rate and the secondary endpoint was the compliance with the recommendations of the care bundle. MEASUREMENT AND RESULTS: Four hundred and forty-five patients (230 and 215 in the observational and intervention periods, respectively) were included. In the two periods, the patients had similar characteristics. The 28-day mortality rate significantly decreased from 40% in the observational period to 27% in the intervention period (P=0.02). According to each recommendation, compliance with the care bundle was achieved in 9 to 100% of patients. CONCLUSION: The implementation of a care bundle adapted from the Surviving Sepsis Campaign guidelines decreases the 28-day mortality rate in patients with severe sepsis and/or septic shock.


Assuntos
Sepse/mortalidade , Choque Séptico/mortalidade , Idoso , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Sepse/prevenção & controle , Índice de Gravidade de Doença , Choque Séptico/prevenção & controle
16.
Bull Cancer ; 97(3): 365-83, 2010 Mar.
Artigo em Francês | MEDLINE | ID: mdl-20176546

RESUMO

HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described. Thus, many other monoclonal antibodies and tyrosine-kinase inhibitors emerged. These therapeutics, used alone or in association with chemotherapy or trastuzumab have variable properties: anti-HER2 and anti-EGFR such as lapatinib, pertuzumab and neratinib; anti-EGFR such as erlotinib and gefitinib; antiangiogenesis (bevacizumab, pazopanib); anti-mTOR pathway (temsirolimus, everolimus) or inhibitor of HSP90 (tanespimycine). In this paper, we present an overview on validated targeted therapies and those which are currently under investigation and seem promising in first line or after progression under trastuzumab. Data regarding cardiotoxicity and the use of trastuzumab under particular clinical circumstances (brain metastases, pregnancy) are also reviewed.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Anastrozol , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzoquinonas/uso terapêutico , Bevacizumab , Neoplasias Encefálicas/secundário , Neoplasias da Mama/química , Neoplasias da Mama/metabolismo , Progressão da Doença , Feminino , Coração/efeitos dos fármacos , Humanos , Lactamas Macrocíclicas/uso terapêutico , Lapatinib , Letrozol , Proteínas de Neoplasias/metabolismo , Nitrilas/uso terapêutico , Quinazolinas/uso terapêutico , Quinolinas/uso terapêutico , Trastuzumab , Triazóis/uso terapêutico
17.
Case Rep Oncol ; 2(3): 177-183, 2009 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-20737034

RESUMO

Carcinomatous meningitis (CM) occurs in 3 to 8% of cancer patients. Patients present with a focal symptom, and multifocal signs are often found following neurological examination. The gold standard for diagnosis remains the demonstration of carcinomatous cells in the cerebrospinal fluid on cytopathological examination. Despite the poor prognosis, palliative treatment could improve quality of life and, in some cases, overall survival. We report on a patient who presented with vertigo, tinnitus and left-sided hearing loss followed by progressive diffuse facial nerve paralysis. Lumbar cerebrospinal fluid confirmed the diagnosis of CM. However, no primary tumor was discovered, even after multiple invasive investigations. This is the first reported case in the English-language medical literature of CM resulting from a carcinoma of unknown primary origin.

18.
Pharmazie ; 61(12): 981-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17283652

RESUMO

This study describes the development and validation of a method for quantification of the antiulcer experimental drug xanthatin in tablets by capillary electrophoresis (CE). Solid oral dosage forms based on xanthatin were designed and assayed on rats. A CE methodology was developed; the parameters evaluated were: background electrolyte composition, concentration and pH, applied voltage and sample preparation. The method was validated in terms of range of linearity, limits of detection (LOD) and quantification (LOQ), accuracy, precision and selectivity and then applied to the pharmaceutical dosage forms. Xanthatin determination was carried out in less than 3 min with a 20 mM sodium tetraborate buffer, pH 9.20. Drug concentration per tablet found was 2.97 +/- 0.2 mg. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, LOD and LOQ were 7.6 and 26 microg mL(-1) respectively. For accuracy evaluation a recovery test was performed, the values being better than 98.6%. With respect to precision, the results obtained were better than 1.02 RSD% (repeatability) and 1.54% (intermediate precision). After the manufacturing process the resulting tablets were biologically active. The methodology developed is useful, simple and rapid for xanthatin determination in tablets.


Assuntos
Antiulcerosos , Furanos/análise , Xanthium/química , Fenômenos Químicos , Físico-Química , Eletroforese Capilar , Etanol , Furanos/isolamento & purificação , Furanos/farmacologia , Indicadores e Reagentes , Controle de Qualidade , Reprodutibilidade dos Testes , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Comprimidos
20.
Phytother Res ; 15(6): 529-31, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11536384

RESUMO

The antiinflammatory activities of ten organic extracts from the aerial parts of Baccharis medullosa DC., Baccharis rufescens S. and Laennecia sophiifolia (Kunth) G. L. Nesom were investigated in mice subjected to carrageenan induced paw oedema. Intraperitoneally administered organic extracts given at doses equivalent to 80 mg/kg of material inhibited the acute phases of inflammation in this model. Our results indicate that the most effective extracts were: n-hexane (I) from B. medullosa, acetone (V) and chloroform (VII) from L. sophiifolia, and acetone (VIII) and chloroform (X) from B. rufescens. All exerted the strongest effect at 5 h after injection of the phlogistic agent.


Assuntos
Anti-Inflamatórios/farmacologia , Asteraceae/química , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Carragenina/farmacologia , Edema/induzido quimicamente , Medicina Herbária , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/uso terapêutico , Estruturas Vegetais
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