RESUMEN
Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.
Asunto(s)
Neoplasias Gastrointestinales/epidemiología , Desnutrición/epidemiología , Estado Nutricional , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Neoplasias Gastrointestinales/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación Nutricional , Apoyo Nutricional/métodos , Pacientes Ambulatorios , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Pérdida de Peso , Adulto JovenRESUMEN
The tolerance and efficacy of oxaliplatin and irinotecan for metastatic colorectal cancer are unknown in elderly patients. Methods. All consecutive patients over 74 years treated with oxaliplatin or irinotecan for metastatic colorectal cancer were enrolled. The tumour response was assessed every 2-3 months and toxicity was collected at each cycle according to World Health Organisation criteria. A total of 66 patients were enrolled from 12 centres. The median age was 78 years (range, 75-88 years); 39 patients had no severe comorbidity according to the Charlson score. In total, 44 and 22 patients received oxaliplatin or irinotecan, respectively, in combination with 5-fluororuracil+/-folinic acid or raltitrexed in 64 patients. A total of 545 chemotherapy cycles were administered in first (41%), second (51%) or third line (8%). A dose reduction occurred in 190 cycles (35%). Complete response, partial response and stabilisation occurred in 1.5, 20 and 47% of patients, respectively. The median time to progression and overall survival were 6.8 and 11.2 months in first line and 6.3 and 11.6 months in second line, respectively. Grade 3 and 4 toxicity occurred in 42% of patients: neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea and vomiting 8% and thrombopenia 6%. There was no treatment-related death. In selected elderly patients, chemotherapy with oxaliplatin or irinotecan is feasible with manageable toxicity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/farmacología , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Quinazolinas/administración & dosificación , Análisis de Supervivencia , Tiofenos/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen. PATIENTS AND METHODS: Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored. RESULTS: Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths. CONCLUSIONS: This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adenocarcinoma/secundario , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Leucovorina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Estudios Prospectivos , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
BACKGROUND: Phosphodiesterase (PDE) inhibitors, among which pentoxifylline (PTX), are candidate molecules for the treatment of TNF-alpha-dependent inflammatory diseases. Based on the controversial effects of PTX observed in experimentally-induced colitis, the aim of this work was to analyse its influence on intestinal epithelial cell proliferation and growth factor expression using the well-established IEC18 cell line. METHODS: The effects of PTX, and of an activation (addition of dibutyryl-cAMP, db-cAMP) or inhibition (by a specific cAMP-protein kinase inhibitor, PKI) of the cAMP pathway, were examined after 3 days of culture. The IEC18 cell proliferation and [3H] thymidine incorporation, as well as the expression of TGF-alpha, TGF-beta1 and -beta2 mRNAs, were analysed in basal culture conditions and in the presence of the pro-inflammatory cytokine, TNF-alpha. RESULTS: PTX, like exogenous db-cAMP, inhibited in a dose-dependent manner the basal and TNF-alpha-modulated IEC18 cell proliferation; this effect was partly prevented by PKI. We confirmed that PTX induced a dose-related increase in intracellular cAMP. Concomitantly, the expression of TGF-alpha mRNA dropped and that of TGF-beta2 increased. Addition of db-cAMP instead of PTX also decreased TGF-alpha mRNA, but did not change TGF-beta2 transcripts. The decrease in the expression of TGF-alpha mRNA caused by PTX and db-cAMP was completely abolished by PKI; in contrast, TGF-beta2 remained unaltered. Yet, anti-TGF-beta2 antibodies partially restored the PTX-inhibited cell proliferation. CONCLUSION: The phosphodiesterase inhibitor, PTX, inhibits IEC18 cell proliferation via a differential modulation of TGF-alpha and TGF-beta2 expression. The drop in TGF-alpha mRNA is related to increasing intracellular cAMP, whereas the effect upon TGF-beta2 appears cAMP-independent.
Asunto(s)
Células Epiteliales/citología , Pentoxifilina/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Factores de Crecimiento Transformadores/biosíntesis , Animales , Bucladesina/farmacología , División Celular/efectos de los fármacos , Línea Celular , AMP Cíclico/metabolismo , Mucosa Intestinal/citología , ARN Mensajero , RatasRESUMEN
OBJECTIVE: Increased nitric oxide (NO) has been demonstrated in inflammatory bowel diseases (IBD). Plasma and urinary nitrite and nitrate are usually considered to reflect global NO generation. Recently it has been suggested that plasma nitrate may be a discriminant indicator between infectious enterocolitis (IC) and IBD. To investigate this hypothesis we compared plasma and 24 h urinary nitrite and nitrate in 13 healthy controls, 44 patients with IBD [Crohn's disease (CD) n = 30; ulcerative colitis (UC) n = 14], 16 patients presenting with IC and seven chronic radiation enterocolitis (RE) patients. RESULTS: Despite a trend towards higher plasma nitrate in IC (54.6+/-11.4 micromol/l) than in the other groups (CD: 38.4+/-4.8, UC: 34.8+/-8.4, RE: 34.7+/-7.5, controls: 31.1+/-5.2), this difference was not statistically significant. Urinary nitrate was higher in IBD, IC and RE than in controls, with no difference between these groups. Nitrite concentrations were not different. Nitrate levels were positively correlated with blood and 24 h urinary neopterin (e.g. plasma nitrate and blood neopterin: r = 0.54, P<0.0001), and in some cases, to C-reactive protein. CONCLUSIONS: High nitrate (in our case only urinary nitrate) appears to be secondary to the magnitude of the inflammation rather than the aetiology of the diarrhoea. It should therefore more likely be considered as a marker of the severity of the inflammatory response rather than used as a discriminant indicator between IC and IBD patients.