Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Ann Oncol ; 33(1): 57-66, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34624497

RESUMEN

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Farmacogenética
3.
Pharmacogenomics J ; 13(2): 159-72, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22158331

RESUMEN

Epithelial ovarian cancer has a poor prognosis owing to late diagnosis and frequent relapse after first-line therapy. Analysis of individual genetic variability could aid in the identification of markers, which could help in stratifying patients with the aim of optimizing individual therapy. In this study we assessed polymorphisms in three genes important in drugs' response in 97 early and 235 late-stage ovarian cancer patients. The Asp1104His polymorphism in xpg, a gene important for removal of platinum adducts, was associated with progression-free survival in early- and late-stage ovarian cancer. Our data indicate that a simple diagnostic analysis such as xpg genotyping can help in predicting response, and extension to other possibly relevant genotypes could be useful in selecting patients with epithelial ovarian cancer for optimal therapy and hence increase the chance of response.


Asunto(s)
Proteínas de Unión al ADN/genética , Endonucleasas/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores Farmacológicos/metabolismo , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Reparación del ADN , Supervivencia sin Enfermedad , Femenino , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Platino (Metal)/administración & dosificación , Platino (Metal)/efectos adversos , Polimorfismo Genético , Pronóstico , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-mdm2/genética , Resultado del Tratamiento
4.
ESMO Open ; 8(1): 100777, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36731325

RESUMEN

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Estudios Prospectivos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/patología , Gemcitabina , Neoplasias Pancreáticas
5.
Br J Cancer ; 107(8): 1227-32, 2012 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-22968651

RESUMEN

BACKGROUND: The most important prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine therapy, and only recently were revalidating in patients receiving targeted therapies (TTs). METHODS: Clinical data for consecutive patients with mRCC who received TTs were retrieved from the database of Istituto Nazionale dei Tumori of Milan. Variables with a significant association with overall survival (OS) were estimated by proportional hazard regression, and a backward stepwise multivariate analysis identified the independent prognostic factors. RESULTS: Data for 336 consecutive patients treated with TTs for RCC during the period 2004-2011 were evaluated. According to the Motzer classification, 32% patients were low risk, 48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42 (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95% CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk classification, Fuhrman grade and previous cytokine therapy were identified as independent prognostic factors (P<0.01). CONCLUSION: The Motzer classification was confirmed as an independent prognostic factor for OS in patients with mRCC receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were independent prognostic factors for clinical outcome.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Renales/clasificación , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia
6.
ESMO Open ; 7(2): 100457, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35366489

RESUMEN

BACKGROUND: Cancer-related fatigue (CRF) is common in patients with advanced solid tumors and several risk factors are described. The possible role of depression is reported by clinicians despite the association with CRF being unclear. MATERIAL AND METHODS: In this monocentric, cross-sectional, prospective study we recruited patients with advanced solid tumors who were hospitalized at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. The primary objective was to assess the correlation between CRF and depression. Secondary objectives were the estimation of CRF and depression prevalence and the identification of associated clinical risk factors. CRF and depression were evaluated through the Functional Assessment of Cancer Therapy-Fatigue subscale and the Zung Self Depression Scale (ZSDS) questionnaires. The Cochran-Armitage trend test was used to demonstrate the primary hypothesis. Univariate and multivariate logistic regression models were used to investigate the impact of clinical variables. RESULTS: A total of 136 patients were enrolled. The primary analysis found a linear correlation (P < 0.0001) between CRF and depression. The prevalence of CRF and of moderate to severe depressive symptoms was 43.5% and 29.2%, respectively. In univariate analysis, patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), anemia, distress, pain, and receiving oncological treatment were at a significantly higher risk for CRF, whereas poor ECOG PS, pain, and distress were risk factors for depression. In multivariate analysis, high levels of ZSDS were confirmed to be correlated to CRF: odds ratio of 3.86 [95% confidence interval (CI) 0.98-15.20) and 11.20 (95% CI 2.35-53.36) for ZSDS of 50-59 and 60-100, respectively (P value for trend 0.002). Moreover, the ECOG PS score was confirmed to be significantly associated with CRF (OR 7.20; 95% CI 1.73-29.96; P = 0.007). CONCLUSIONS: Our data suggest a strong correlation between CRF and depression in patients with advanced solid tumors. Further investigations are needed to better understand this relationship and if depressive disorder therapeutic strategies could also impact on CRF.


Asunto(s)
Depresión , Neoplasias , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Fatiga/epidemiología , Fatiga/etiología , Humanos , Neoplasias/complicaciones , Neoplasias/epidemiología , Dolor/complicaciones , Estudios Prospectivos , Calidad de Vida
7.
J Med Ethics ; 34(10): 747-50, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18827108

RESUMEN

AIMS AND BACKGROUND: The present work assessed the impact of two decrees on ethics committees in Italy, aimed at bringing the national laws on the conduct of clinical trials into line with the rest of the EC, and regulating and facilitating not-for-profit research. MATERIAL AND METHODS: Prospectively collected data from an Italian multicentre study were examined with respect to the ethics review process. Administrative and time elements of the review process were audited. Main outcome measures were time between the application submission and the ethics committee definitive opinion, type and number of application submission forms, number of ethics committees that refused fee exemption, and time between the ethics committee approval and the administrative authorisation. RESULTS: A total of 134 local research ethics committees (LRECs) were approached. Application submission procedures and application forms varied greatly; paper submission was mandatory. The median time from submission to approval was 72 days. Only two LRECs refused the fee exemption. The median time from LREC approval to administrative agreement was 50 days and only 9.6% of local authorities came to a verbal agreement with the sponsor. CONCLUSIONS: Italian LRECs are still not sufficiently efficient in complying with the Directive 2001/20/EC requirement (60 days). Better coordination of LRECs work is needed although the optimal level of coordination between them is still not known. In the meantime, national guidelines are needed concerning the application of Directive 2001/20/EC. The behaviour of Italian LRECs towards not-for-profit research was excellent although only the fee exemption was requested.


Asunto(s)
Investigación Biomédica/legislación & jurisprudencia , Comités de Ética/legislación & jurisprudencia , Investigación Biomédica/ética , Investigación Biomédica/normas , Comités de Ética/ética , Comités de Ética/normas , Regulación Gubernamental , Guías como Asunto/normas , Italia
8.
Biochem Pharmacol ; 144: 52-62, 2017 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-28782526

RESUMEN

Trabectedin and its analogue lurbinectedin are effective drugs used in the treatment of ovarian cancer. Since the presence of ascites is a frequent event in advanced ovarian cancer we asked the question whether ascites could modify the activity of these compounds against ovarian cancer cells. The cytotoxicity induced by trabectedin or lurbinectedin against A2780, OVCAR-5 cell lines or primary culture of human ovarian cancer cells was compared by performing treatment in regular medium or in ascites taken from either nude mice or ovarian cancer patients. Ascites completely abolished the activity of lurbinectedin at up to 10nM (in regular medium corresponds to the IC90), strongly reduced that of trabectedin, inhibited the cellular uptake of lurbinectedin and, to a lesser extent, that of trabectedin. Since α1-acid glycoprotein (AGP) is present in ascites at relatively high concentrations, we tested if the binding of the drugs to this protein could be responsible for the reduction of their activity. Adding AGP to the medium at concentration range of those found in ascites, we reproduced the anticytotoxic effect of ascites. Erythromycin partially restored the activity of the drugs, presumably by displacing them from AGP. Equilibrium dialysis experiments showed that both drugs bind AGP, but the affinity of binding of lurbinectedin was much greater than that of trabectedin. KD values are 8±1.7 and 87±14nM for lurbinectedin and trabectedin, respectively. The studies intimate the possibility that AGP present in ascites might reduce the activity of lurbinectedin and to a lesser extent of trabectedin against ovarian cancer cells present in ascites. AGP plasma levels could influence the distribution of these drugs and thus they should be monitored in patients receiving these compounds.


Asunto(s)
Ascitis/metabolismo , Carbolinas/metabolismo , Dioxoles/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/metabolismo , Orosomucoide/metabolismo , Neoplasias Ováricas/metabolismo , Tetrahidroisoquinolinas/metabolismo , Animales , Antineoplásicos Alquilantes/metabolismo , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Carbolinas/farmacología , Carbolinas/uso terapéutico , Línea Celular Tumoral , Dioxoles/farmacología , Dioxoles/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Humanos , Ratones , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Unión Proteica/fisiología , Tetrahidroisoquinolinas/farmacología , Tetrahidroisoquinolinas/uso terapéutico , Trabectedina , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
9.
Crit Rev Oncol Hematol ; 104: 9-20, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27286698

RESUMEN

Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma , Neoplasias Pleurales , Animales , Humanos , Incidencia , Italia/epidemiología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Mesotelioma/complicaciones , Mesotelioma/diagnóstico , Mesotelioma/epidemiología , Mesotelioma/terapia , Mesotelioma Maligno , Derrame Pleural/etiología , Neoplasias Pleurales/complicaciones , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/terapia , Salud Pública , Factores de Riesgo
10.
Biochim Biophys Acta ; 1531(1-2): 111-31, 2001 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-11278177

RESUMEN

The high resolution proton nuclear magnetic resonance (1H-NMR) spectra of two different cell lines exhibiting multidrug resistance (MDR) as demonstrated by the expression of the well-known energy-driven, membrane-bound 170 kDa P-glycoprotein pump known as Pgp were investigated. In particular, the mobile lipid (ML) profile, and the growth and biochemical characteristics of MCF-7 (human mammary carcinoma) and LoVo (human colon adenocarcinoma) sensitive and resistant tumor cells were compared. The results indicate that both MCF-7 and LoVo resistant cells have a higher ML intensity than their respective sensitive counterparts. However, since sensitive and resistant cells of each pair grow in the same manner, variations in growth characteristics do not appear to be the cause of the ML changes as has been suggested by other authors in non-resistant tumor cells. In order to investigate further the origin of the ML changes, lipid analyses were conducted in sensitive and resistant cell types. The results of these experiments show that resistant cells of both cell types have a greater amount of esterified cholesterol and saturated cholesteryl ester and triglyceride fatty acid than their sensitive counterparts. From a thorough analysis of the data obtained in this paper utilizing numerous techniques including biological, biophysical and biochemical ones, it is hypothesized that cholesterol and triglyceride play a pivotal role in inducing changes in NMR ML signals. The importance of these lipid variations in MDR is discussed in view of the controversy regarding the origin of ML signals and the paramount role played by the Pgp pump in resistance.


Asunto(s)
Colesterol/química , Resistencia a Múltiples Medicamentos , Lípidos/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/química , Ciclo Celular , Ésteres del Colesterol/química , Ácidos Grasos/análisis , Ácidos Grasos Insaturados/análisis , Colorantes Fluorescentes , Humanos , Espectroscopía de Resonancia Magnética/métodos , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Oxazinas , Fosfolípidos/análisis , Triglicéridos/química , Células Tumorales Cultivadas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA