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1.
Water Sci Technol ; 82(11): 2513-2524, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33339804

ABSTRACT

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.


Subject(s)
Charcoal , Water Pollutants, Chemical , Adsorption , Clofibric Acid , Hydrogen-Ion Concentration , Kinetics , Phosphoric Acids , Spectroscopy, Fourier Transform Infrared , Water Pollutants, Chemical/analysis
2.
Gynecol Oncol ; 158(3): 666-672, 2020 09.
Article in English | MEDLINE | ID: mdl-32624235

ABSTRACT

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.


Subject(s)
Neoplasms, Germ Cell and Embryonal/therapy , Ovarian Neoplasms/therapy , Watchful Waiting , Adolescent , Adult , Aged , Choriocarcinoma/drug therapy , Choriocarcinoma/pathology , Choriocarcinoma/surgery , Choriocarcinoma/therapy , Dysgerminoma/drug therapy , Dysgerminoma/pathology , Dysgerminoma/surgery , Dysgerminoma/therapy , Endodermal Sinus Tumor/drug therapy , Endodermal Sinus Tumor/pathology , Endodermal Sinus Tumor/surgery , Endodermal Sinus Tumor/therapy , Female , Humans , Middle Aged , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Prognosis , Retrospective Studies , Teratoma/drug therapy , Teratoma/pathology , Teratoma/surgery , Teratoma/therapy , Young Adult
3.
Cancer Radiother ; 24(4): 279-287, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32439358

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy/methods , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy/adverse effects , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Female , Follow-Up Studies , Humans , Induction Chemotherapy/methods , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local , Radiotherapy Dosage , Retrospective Studies , Survival Rate , Time Factors , Treatment Outcome
4.
Ann Oncol ; 31(2): 289-294, 2020 02.
Article in English | MEDLINE | ID: mdl-31959346

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Melanoma , Bayes Theorem , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome , Vemurafenib/therapeutic use
5.
Lupus ; 28(5): 642-650, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30907294

ABSTRACT

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.


Subject(s)
Caregivers/psychology , Lupus Erythematosus, Systemic/physiopathology , Lupus Erythematosus, Systemic/psychology , Self-Management , Adolescent , Age of Onset , Child , Female , Focus Groups , Humans , Interviews as Topic , Lupus Erythematosus, Systemic/therapy , Male , Ohio , Patient Compliance , Quality of Life , Registries , Surveys and Questionnaires , Young Adult
6.
Rev Medisan ; 22(9)2018.
Article in Spanish | CUMED | ID: cum-79338

ABSTRACT

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]


Subject(s)
Humans , Respiratory Insufficiency , Prognosis , Mortality , Respiration, Artificial , Critical Care
7.
Nat Commun ; 8: 15228, 2017 05 09.
Article in English | MEDLINE | ID: mdl-28485400

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-28072765

ABSTRACT

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.


Subject(s)
Aminopyridines/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Endometrioid/drug therapy , Endometrial Neoplasms/drug therapy , Morpholines/therapeutic use , Aged , Aged, 80 and over , Carcinoma, Endometrioid/pathology , Chemotherapy, Adjuvant , Disease Progression , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Phosphoinositide-3 Kinase Inhibitors , Recurrence , Treatment Outcome
9.
Ann Oncol ; 25(11): 2191-2196, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25210017

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Thalidomide/analogs & derivatives , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , CA-125 Antigen/blood , Carcinoma, Ovarian Epithelial , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/pathology , Fallopian Tube Neoplasms , Female , Humans , Lenalidomide , Membrane Proteins/blood , Middle Aged , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasms, Glandular and Epithelial/blood , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/blood , Ovarian Neoplasms/pathology , Platinum/adverse effects , Thalidomide/administration & dosage , Thalidomide/adverse effects
11.
Br J Cancer ; 108(9): 1771-7, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23612453

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Endometrial Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Aged , Antineoplastic Agents/adverse effects , Disease-Free Survival , Drug Resistance, Neoplasm , Everolimus , Female , Humans , Middle Aged , Sirolimus/adverse effects , Sirolimus/therapeutic use , Survival Rate
12.
Br J Cancer ; 107(4): 598-603, 2012 Aug 07.
Article in English | MEDLINE | ID: mdl-22790797

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Neoplasms/drug therapy , Recombinant Fusion Proteins/administration & dosage , Taxoids/administration & dosage , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Docetaxel , Drug Administration Schedule , Fatigue/chemically induced , Female , Humans , Male , Middle Aged , Neutropenia/chemically induced , Receptors, Vascular Endothelial Growth Factor
13.
Ann Oncol ; 22(2): 321-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20693300

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Genes, erbB-2 , Breast Neoplasms/genetics , Cohort Studies , Female , Follow-Up Studies , Humans
14.
Br J Cancer ; 103(9): 1335-42, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20978512

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Genes, erbB-2 , Adult , Aged , Antibodies, Monoclonal, Humanized , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Disease-Free Survival , Female , Gene Amplification , Humans , Middle Aged , Neoadjuvant Therapy , Remission Induction , Trastuzumab
15.
Ann Fr Anesth Reanim ; 29(9): 621-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20634026

ABSTRACT

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.


Subject(s)
Sepsis/mortality , Shock, Septic/mortality , Aged , Female , Guideline Adherence , Humans , Male , Middle Aged , Practice Guidelines as Topic , Prospective Studies , Retrospective Studies , Sepsis/prevention & control , Severity of Illness Index , Shock, Septic/prevention & control
16.
Bull Cancer ; 97(3): 365-83, 2010 Mar.
Article in French | MEDLINE | ID: mdl-20176546

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Anastrozole , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzoquinones/therapeutic use , Bevacizumab , Brain Neoplasms/secondary , Breast Neoplasms/chemistry , Breast Neoplasms/metabolism , Disease Progression , Female , Heart/drug effects , Humans , Lactams, Macrocyclic/therapeutic use , Lapatinib , Letrozole , Neoplasm Proteins/metabolism , Nitriles/therapeutic use , Quinazolines/therapeutic use , Quinolines/therapeutic use , Trastuzumab , Triazoles/therapeutic use
17.
Case Rep Oncol ; 2(3): 177-183, 2009 Oct 10.
Article in English | MEDLINE | ID: mdl-20737034

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-17283652

ABSTRACT

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.


Subject(s)
Anti-Ulcer Agents , Furans/analysis , Xanthium/chemistry , Chemical Phenomena , Chemistry, Physical , Electrophoresis, Capillary , Ethanol , Furans/isolation & purification , Furans/pharmacology , Indicators and Reagents , Quality Control , Reproducibility of Results , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Tablets
20.
Phytother Res ; 15(6): 529-31, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11536384

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Asteraceae/chemistry , Edema/drug therapy , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/therapeutic use , Carrageenan/pharmacology , Edema/chemically induced , Herbal Medicine , Male , Mice , Phytotherapy , Plant Extracts/therapeutic use , Plant Structures
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