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1.
Clin Transl Oncol ; 21(2): 232-238, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29968135

RESUMEN

AIM: To study the prognostic factors of gastric cancer (GC) patients who were classified with stage III disease according to the newest TNM classification. METHODS: This study retrospectively enrolled 279 patients who underwent radical gastrectomy from January 2012 to December 2014 at our hospital and who were diagnosed with stage III GC according to the new 8th edition of the TNM classification. The patient data that were collected included age, sex, pathological parameters, survival, lymph node ratio, neo-adjuvant chemotherapy with oxaliplatin and S-1, and operation type. The characteristics, survival, and prognostic factors of the patients were analyzed by univariate and multivariate analyses. RESULTS: The median OS of the patients after curative surgery was 19 months, and the 3-year survival rate (3-YSR) was 25.3%. A univariate analysis showed that tumor location (P = 0.01), neo-adjuvant chemotherapy (P = 0.005), pathological T stage (P = 0.002), pathological N stage (P < 0.001), lymph node ratio (LNR) (P < 0.001), and operation type (P = 0.032) were significantly associated with overall survival. A multivariate analysis revealed that neo-adjuvant chemotherapy (P = 0.009), pathological T stage (P = 0.012), and LNR (P < 0.001) were independent prognostic factors. CONCLUSIONS: Neo-adjuvant chemotherapy, pathological T stage, and LNR were independent prognostic factors for the overall survival of patients with stage III GC. The neo-adjuvant chemotherapy with oxaliplatin and S-1 can be used for the patients to improve their survival.


Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Estadificación de Neoplasias/métodos , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Adenocarcinoma/clasificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/mortalidad , Combinación de Medicamentos , Femenino , Gastrectomía/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/mortalidad , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/clasificación , Tegafur/administración & dosificación
2.
Oncotarget ; 7(11): 12672-81, 2016 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-26862857

RESUMEN

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. PATIENTS AND METHODS: This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. RESULTS: 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. CONCLUSIONS: Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/terapia , Quimioradioterapia/métodos , MicroARNs/sangre , Neoplasias Pancreáticas/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/mortalidad , Cetuximab/administración & dosificación , Cetuximab/efectos adversos , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Tegafur , Uracilo , Gemcitabina
3.
Clin Transl Oncol ; 18(4): 413-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26304854

RESUMEN

BACKGROUND: In the present study, we compared the efficacy and safety of concurrent radiotherapy with S-1 plus cisplatin (CRSC) versus concurrent radiotherapy with cisplatin alone (CRC) for the treatment of advanced cervical carcinoma (ACC). METHODS: Between February 2006 and January 2009, 72 eligible patients with ACC were included and randomly divided into two groups. Thirty-six patients received CRSC with radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1, S-1 (according to body surface area) for 28 days repeated every 6 weeks, and cisplatin (50 mg/m(2), intravenously on day 1) every 4 weeks for two cycles. The other 36 received CRC at the same cisplatin and radiotherapy dosage as for CRSC. The primary outcome was overall survival, whereas the secondary outcomes included progression-free survival and toxicity. RESULTS: The median overall survival was 75 months (range 4-86 months) for the CRSC group and 66 months (range 3-87 months) for the CRC group (P = 0.039). The median corresponding progression-free survival was 66 months (range 3-75 months) and 58 months (range 3-71 months), respectively (P = 0.042). The toxicity profile was similar in both the groups. CONCLUSION: Our results suggested that CRSC might be more effective than CRC in patients with ACC with acceptable toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias del Cuello Uterino/terapia , Cisplatino/administración & dosificación , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Proyectos Piloto , Pronóstico , Dosificación Radioterapéutica , Tasa de Supervivencia , Tegafur/administración & dosificación , Neoplasias del Cuello Uterino/patología
4.
Clin Transl Oncol ; 18(7): 672-6, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26482723

RESUMEN

BACKGROUND: This study aimed to investigate the safety and efficacy of S-l combined with cisplatin plus concurrent chemoradiotherapy (SCCC) versus cisplatin plus concurrent chemoradiotherapy (CCC) for Chinese patients with advanced gastric cancer (AGC). METHODS: Between April 2008 and June 2010, 144 eligible patients with AGC were included and divided randomly into 2 groups. Seventy-two patients in the SCCC group received with S-1 on days 1-14 of a 21-day cycle, 24-h cisplatin infusion (70 mg/m(2) on day 1) every 4 weeks for 2 cycles, and concurrent chemoradiotherapy (30-Gy radiotherapy over 4 weeks) beginning on day 1. The other 72 patients in the CCC group were administered cisplatin and concurrent chemoradiotherapy as for SCCC. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: The median overall survival durations were 11.7 months (range 1.7-29.7 months) and 9.5 months (range 1.2-25.4 months) in SCCC and CCC groups, respectively (P = 0.041). The median progression-free survival durations were 10.6 months for SCCC (range 1.3-24.7 months) and 8.8 months (range 0.7-22.3 months) for CCC (P = 0.046). The toxicity profile was similar in both groups. CONCLUSION: In summary, SCCC showed more promising safety and efficacy than CCC in Chinese patients with AGC. In addition, the toxicities were also acceptable in both groups.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/terapia , Tegafur/administración & dosificación , Adulto , Anciano , Pueblo Asiatico , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/mortalidad , Resultado del Tratamiento , Adulto Joven
5.
Genet Mol Res ; 13(4): 10952-7, 2014 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-25526216

RESUMEN

Gastric cancer is the fourth most common cancer worldwide and the leading cause of tumor-related death in China. Gastric cancer is a heterogeneous disease and therefore requires different treatments based on the subtype. We describe a patient who had gastric cancer with liver metastases. Biopsy and tumor analysis using the HercepTest revealed a human epidermal growth factor receptor 2 (HER2)-positive adenocarcinoma as confirmed by fluorescence in situ hybridization. The patient was treated with a regimen of trastuzumab, oxaliplatin, and S-1 (six cycles). When positron emission tomography findings suggested that the metastases had resolved, the patient underwent surgery. Histopathologically, no cancer cells were observed in the resected hepatic tissue. The patient underwent tumor resection surgery, during which the tumor and gastric lymph nodes with lesions were removed. The patient has remained disease-free for 3 months. Therefore, trastuzumab may be an effective agent in the chemotherapeutic treatment of liver metastases in patients with HER2-positive gastric adenocarcinoma.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/secundario , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Combinación de Medicamentos , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Ácido Oxónico/administración & dosificación , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Trastuzumab , Resultado del Tratamiento
6.
J. bras. nefrol ; 36(4): 535-541, Oct-Dec/2014. tab
Artículo en Portugués | LILACS | ID: lil-731148

RESUMEN

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.


Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.


Asunto(s)
Animales , Femenino , Humanos , Ratones , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Oxidorreductasas/antagonistas & inhibidores , Paclitaxel/administración & dosificación , Pirimidinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Dihidrouracilo Deshidrogenasa (NADP) , Floxuridina/administración & dosificación , Floxuridina/farmacología , Ratones Endogámicos ICR , Trasplante de Neoplasias , Tegafur/administración & dosificación , Tegafur/farmacología , Uracilo/administración & dosificación , Uracilo/farmacología
7.
Rev. bras. enferm ; Rev. bras. enferm;67(6): 886-890, Nov-Dec/2014. tab
Artículo en Portugués | LILACS, BDENF - Enfermería | ID: lil-732809

RESUMEN

Objetivou-se identificar comportamentos e práticas sexuais de homens que fazem sexo com homens no contexto da vulnerabilidade ao HIV/AIDS. Estudo transversal, exploratório descritivo. Foi realizado em um local de sociabilidade gay de Fortaleza, no Estado do Ceará, entre novembro de 2010 e março de 2011, por meio de entrevista com 189 homens que fazem sexo com homens. Encontrou-se uma amostra composta, majoritariamente, por jovens, solteiros e com alto nível educacional. A história sexual demonstrou o início precoce da vida sexual, com prevalência elevada de relação sexual com parceira do sexo oposto. Houve alta frequência de testagem para o HIV. As práticas sexuais revelaram prevalência superior da realização de sexo oral e anal, bem como altos níveis de proteção no sexo anal, apesar de baixa no sexo oral. Constatou-se uma maior incorporação das práticas de prevenção em relação ao panorama nacional do início da epidemia.


The objective was to identify behaviors and sexual practices of men who have sexual relations with other men in the context of vulnerability to HIV/AIDS. This was a cross-sectional, exploratory and descriptive study. It was carried out in a gay sociability place in Fortaleza, Ceará, Brazil, between November 2010 and March 2011, through interviews with 189 men who have sex with men. The ethical aspects were respected. We found a sample consisting mostly by young, single, and highly educated men. The sexual history demonstrated the early onset of sexual activity, with a high prevalence of sexual intercourse with a partner of the opposite sex. There was also a high prevalence of HIV testing. Sexual practices revealed high prevalence of performing oral and anal sex, as well as high levels of protection in anal sex, despite the low protection in oral sex. A greater incorporation of prevention practices was found compared to the national scene in the beginning of the disease outbreak.


El objetivo fue identificar los comportamientos y las prácticas sexuales de los hombres que tienen sexo con hombres en el contexto de la vulnerabilidad al VIH/SIDA. Fue un estudio transversal, descriptivo y exploratorio. Se celebró en una sociabilidad local gay de Fortaleza, Ceará, Brasil, entre noviembre de 2010 y marzo de 2011, a través de entrevistas con 189 hombres que tienen sexo con hombres. Se encontró una muestra compuesta en su mayoría por jóvenes, solteros y con alto nivel de educación. La historia sexual demostró el inicio temprano de la actividad sexual, la alta prevalencia de relaciones sexuales con una pareja del sexo opuesto. Hubo alta prevalencia de la prueba del VIH. Las prácticas sexuales revelaron una alta prevalencia de realizar sexo oral y anal, así como altos niveles de protección en el sexo anal, a pesar de la baja protección en el sexo oral. Se encontró una mayor incorporación de las prácticas de prevención en relación con la escena nacional en el inicio de la epidemia.


Asunto(s)
Animales , Femenino , Ratas , Fluorouracilo/farmacocinética , Hígado/efectos de los fármacos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Tumor Carcinoide/tratamiento farmacológico , Tumor Carcinoide/metabolismo , Floxuridina/farmacocinética , Floxuridina/uso terapéutico , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Infusiones Intravenosas , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Neoplasias Experimentales/tratamiento farmacológico , Ratas Endogámicas , Tegafur/farmacocinética , beta-Alanina/análisis , beta-Alanina/análogos & derivados , beta-Alanina/biosíntesis
8.
Rev. latinoam. enferm ; Rev. latinoam. enferm. (Online);22(6): 988-993, 16/12/2014.
Artículo en Inglés | LILACS, BDENF - Enfermería | ID: lil-732949

RESUMEN

OBJECTIVE: to propose a discussion about traces of the derivation of meanings, the subjects' discomfort and resistance when they are called upon to signify a questionnaire on the transfer of the Directly Observed Treatment of Tuberculosis policy, in order to reveal the limitations of closed questionnaires in the subject's interpretation process. METHOD: health professionals from a Primary Health Care Unit in Porto Alegre/RS were interviewed and some excerpts from the interviews were investigated in the light of French Discourse Analysis. RESULTS: resistance, discomfort, slips, silencing and the derivation of meanings were observed in the subjects' interpretation. CONCLUSION: the interpretation process has multiple meanings and varies from subject to subject. The questionnaire, as a prototype of the logically stabilized universe, fails when the purpose is to control the interpretation. Its isolated use in health research can entail inexactness or incompleteness of the collected data. Therefore, its use associated with qualitative research techniques is ideal. .


OBJETIVO: propor uma discussão a respeito de vestígios da derivação de sentidos, do desconforto e resistência dos sujeitos, quando convocados a significar um questionário referente à transferência da política do tratamento diretamente observado da tuberculose, de modo a revelar as limitações de questionários fechados, quando se trata do processo interpretativo do sujeito. MÉTODO: profissionais de saúde de uma Unidade de Atenção Primária de Saúde de Porto Alegre, RS, foram entrevistados e alguns recortes das entrevistas examinados à luz da Análise de Discurso de linha francesa. RESULTADOS: observou-se a resistência, o incômodo, o deslizamento, o silenciamento e a derivação dos sentidos no ato de interpretação dos sujeitos. CONCLUSÃO: o processo de interpretação é polissêmico e varia de sujeito para sujeito. O questionário, enquanto um protótipo do universo logicamente estabilizado, falha quando o propósito é o de controlar a interpretação. O seu uso de forma isolada, em pesquisas em saúde, pode incorrer em inexatidão ou incompletude dos dados obtidos, sendo ideal a sua utilização associada a técnicas qualitativas de pesquisa. .


OBJETIVO: proponer una discusión respecto a vestigios de la derivación de sentidos, del malestar y resistencia de los sujetos cuando convocados a significar un cuestionario respecto a la trasferencia de la política del Tratamiento Directamente Observado de la Tuberculosis, de manera a revelar las limitaciones de cuestionarios cerrados cuando se trata del proceso interpretativo del sujeto. MÉTODO: profesionales de salud de una Unidad de Atención Primaria de Salud de Porto Alegre/RS fueron entrevistados y algunos recortes de las entrevistas examinados a la luz del Análisis de Discurso de línea Francesa. RESULTADOS: fueron observados la resistencia, la molestia, el deslizamiento, el silenciamiento y la derivación de los sentidos en el acto de interpretación de los sujetos. CONCLUSIÓN: el proceso de interpretación es polisémico y varia de sujeto a sujeto. El cuestionario como un prototipo del universo lógicamente estabilizado falla cuando el objetivo es el de controlar la interpretación. Su uso de forma aislada en investigaciones en salud puede llevar a datos inexactos o incompletos, siendo ideal su utilización asociada a técnicas cualitativas de investigación. .


Asunto(s)
Animales , Masculino , Ratones , Antineoplásicos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Floxuridina/uso terapéutico , Fluorouracilo/uso terapéutico , Plasmacitoma/tratamiento farmacológico , Tegafur/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Intoxicación por Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Fluorouracilo/análogos & derivados , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Plasmacitoma/complicaciones , Uracilo/uso terapéutico
9.
Invest Clin ; 55(2): 185-202, 2014 Jun.
Artículo en Español | MEDLINE | ID: mdl-24974634

RESUMEN

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.


Asunto(s)
Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/clasificación , Transporte Biológico/genética , Biomarcadores , Biotransformación/genética , Capecitabina , Terapia Combinada , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Resistencia a Antineoplásicos/genética , Enzimas/genética , Etnicidad/genética , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacocinética , Fluorouracilo/uso terapéutico , Gastrectomía , Humanos , México , Terapia Molecular Dirigida , Compuestos Organoplatinos/farmacocinética , Ácido Oxónico/farmacocinética , Selección de Paciente , Farmacogenética , Medicina de Precisión , Profármacos/farmacocinética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Tegafur/farmacocinética
10.
Invest. clín ; Invest. clín;55(2): 185-202, jun. 2014. ilus, tab
Artículo en Español | LILACS | ID: lil-749976

RESUMEN

Debido a la inespecificidad de los síntomas, el cáncer gástrico (CG) es diagnosticado frecuentemente en etapas avanzadas, lo que da cuenta de los altos índices de mortalidad debido a esta neoplasia a nivel mundial. El esquema de tratamiento adyuvante o neoadyuvante en los países occidentales incluye el uso de fluoropirimidinas citotóxicas y compuestos de platino formadores de aductos en el ADN. La respuesta clínica al tratamiento con estos fármacos depende principalmente de la sensibilidad del tumor, la cual a su vez está condicionada por el nivel de expresión de los blancos terapéuticos y de las enzimas de reparación del ADN. Sumado a esto, algunos polimorfismos de línea germinal en genes asociados al metabolismo y a la respuesta a estos fármacos, han mostrado asociación con respuestas pobres y con el desarrollo de eventos adversos, incluso con resultados fatales. La identificación de biomarcadores genómicos, en la forma de polimorfismos genéticos o la expresión diferencial de genes específicos asociados a la respuesta quimioterapeútica ha sido motivo de intensa investigación como base para la aplicación de la farmacogenómica en el establecimiento de una terapia farmacológica racional y personalizada del CG. Sin embargo, ante la eventual aplicación de la farmacogenómica en el ámbito clínico, es necesario establecer el valor pronóstico real de dichos biomarcadores mediante los estudios de asociación genotipo-fenotipo, así como su prevalencia en el contexto de cada población de pacientes. Estos aspectos son indispensables al evaluar la relación costo-efectividad de la introducción de los productos de la medicina genómica predictiva en el tratamiento del CG.


Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.


Asunto(s)
Humanos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/clasificación , Biomarcadores , Transporte Biológico/genética , Biotransformación/genética , Terapia Combinada , Combinación de Medicamentos , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Resistencia a Antineoplásicos/genética , Enzimas/genética , Etnicidad/genética , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacocinética , Fluorouracilo/uso terapéutico , Gastrectomía , México , Terapia Molecular Dirigida , Compuestos Organoplatinos/farmacocinética , Ácido Oxónico/farmacocinética , Selección de Paciente , Farmacogenética , Medicina de Precisión , Profármacos/farmacocinética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Tegafur/farmacocinética
11.
Clin Transl Oncol ; 15(10): 836-42, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23381898

RESUMEN

PURPOSE: This randomized phase II study was conducted to compare the efficacy and safety of paclitaxel with S-1 (PS) vs. S-1 in patients with advanced gastric cancer (AGC). METHODS: Eighty-two (82) patients were 1:1 randomly assigned to oral S-1 (daily for 2 weeks, every 4 weeks' cycle) or S-1 (daily for 2 weeks, every 4 weeks' cycle) plus paclitaxel (on day 1, 8 and 15 of a 4 weeks' cycle). S-1 was orally administered with a fixed quantity according to body surface area (BSA), while paclitaxel was given 60 mg/m(2) i.v. daily through an implanted catheter. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall responsible rates and safety. RESULTS: The median OS with PS versus S-1 monotherapy was 14.0 versus 11.0 months (P = 0.02), survival at 12 months was 61.0 % in the PS group and 46.3 % in the S-1 group. Median PFS was also significantly longer in the PS group (6.0 months) than in the S-1 group (4.0 months). The overall response rate was determined in 82 evaluable patients, and was significantly higher (P = 0.04) with PS (19 patients, 46.3 %) than with S-1 monotherapy (10 patients, 24.4 %). PS was well tolerated with no treatment-related deaths, all were grade 3-4 gastrointestinal toxicities, including anorexia, nausea, and diarrhea developed in less than 10 % of the patients. CONCLUSIONS: Combination chemotherapy of paclitaxel with S-1 is well tolerated and active in AGC patients. Further investigation with comparative trials is needed for confirmation.


Asunto(s)
Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/mortalidad , Neoplasias Peritoneales/mortalidad , Neoplasias Gástricas/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Combinación de Medicamentos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Tegafur/administración & dosificación , Adulto Joven
12.
Rev. salud pública ; Rev. salud pública;16(3): 371-381, 2012. ilus, tab
Artículo en Español | LILACS | ID: lil-729648

RESUMEN

Objetivo Construir desde la comunidad una propuesta educativa orientada al auto empoderamiento para mejorar las condiciones sanitarias y de habitabilidad de la vivienda. Método Con un enfoque constructivista y con base en el programa "Gestores comunitarios del hábitat", se trabajó con quince familias residentes en el barrio Mochuelo Bajo de la Localidad de Ciudad Bolívar en Bogotá, Colombia, con el fin de que identificaran los aspectos sanitarios más relevantes para el mejoramiento de sus viviendas y propusieran la metodología y organización de la propuesta educativa. Resultados Se identificaron veinti ún indicadores epidemiológicos ligados a una vivienda insalubre, los cuales sirvieron como base para definir las problemáticas específicas y establecer la metodología para diseñar la propuesta educativa. Discusión El curso diseñado pretende fomentar la educación y las capacidades en salud de la comunidad con el fin de mejorar las condiciones de habitabilidad de las viviendas y lograr un entorno saludable del hábitat que les permita desarrollarse con bienestar y dignidad.


Objective This was a community-based effort at constructing an educational proposal orientated towards self-empowerment aimed at improving the target population's sanitary, housing and living conditions through cooperative learning. Methods A constructivist approach was adopted based on a programme called "Habitat community manger". The project involved working with fifteen families living in the Mochuelo Bajo barrio in Ciudad Bolívar in Bogotá, Colombia, for identifying the most relevant sanitary aspects for improving their homes and proposing a methodology and organisation for an educational proposal. Results Twenty-one poor housing-related epidemiological indicators were identified which formed the basis for defining specific problems and establishing a methodology for designing an educational proposal. Discussion The course which emerged from the cooperative learning experience was designed to promote the community's skills and education regarding health aimed at improving households' living conditions and ensuring a healthy environment which would allow them to develop an immediate habitat ensuring their own welfare and dignity.


Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Esquema de Medicación , Combinación de Medicamentos , Floxuridina/administración & dosificación , Japón , Metotrexato/administración & dosificación , Mitomicina/administración & dosificación , Análisis de Supervivencia , Tegafur/administración & dosificación , Uracilo/administración & dosificación
13.
Clin Transl Oncol ; 13(7): 480-4, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21775275

RESUMEN

PURPOSE: To analyse results of combined treatment of adjuvant radio-chemotherapy (RT-CT) in patients diagnosed with gallbladder cancer (GBC) after complete resection. METHODS AND MATERIAL: From June 1993 until July 2006, 67 patients with a diagnosis of GBC who underwent R0 surgical resection and were staged as T1b-2-3N0-1M0 received adjuvant RT-CT. Radiotherapy consisted of whole abdominal irradiation (20 Gy at 100 cGy daily) plus a boost to the tumour bed for a total of 45-59.4 Gy. Concomitant chemotherapy (fluoropyrimidines) was given. Overall survival (OS) and median survival were analysed in relation to different prognostic factors. RESULTS: With a median follow-up of 90 months, 5-year OS was 41%, in the group who underwent extended cholecystectomy it reached 57% and it was only 27% in those who underwent simple cholecystectomy (p = 0.005). Median survival was 42 months for the whole population, not yet reached for the extended cholecystectomy subgroup and 23 months for the simple cholecystectomy subgroup. When analysing for histological grade, median survival was 23 months for those graded as high grade (III or IV) and 57 months for those of low-unknown grade (p = 0.029). In multivariate analysis, a statistically significant OS benefit was found for those who underwent extended cholecystectomy (p = 0.003). CONCLUSIONS: In the absence of randomised studies, these data support the use of extended cholecystectomy followed by adjuvant RT-CT in patients diagnosed as stages T1b-2- 3N0-1M0 GBC after R0 resection.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Colecistectomía , Neoplasias de la Vesícula Biliar/terapia , Adulto , Anciano , Anciano de 80 o más Años , Capecitabina , Quimioterapia Adyuvante , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Tasa de Supervivencia , Tegafur/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificación , Gemcitabina
14.
Clin Transl Oncol ; 13(4): 281-6, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21493190

RESUMEN

INTRODUCTION: To assess the efficacy and safety profile of biweekly vinorelbine and tegafur/uracil (UFT) as treatment in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Patients with histologically confirmed breast cancer, measurable disease, no more than one prior chemotherapy regimen for metastatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and adequate bone marrow, renal and liver function were eligible. Patients received vinorelbine (30 mg/m(2) on day 1) and UFT (250 mg/m(2) daily) every two weeks for 12 cycles unless progression or unacceptable toxicity was observed. RESULTS: Thirty-seven patients were included and received 311 cycles of chemotherapy. Efficacy and toxicity analyses were carried out on an intention-to-treat basis. The overall response rate was 35% (95% CI: 20-53). With a median follow-up of 18.6 months (95% CI: 1.0-74.3), the median time to progression was 7.0 months (96% CI: 5.2-8.9) and the median overall survival was 19.4 months (95% CI: 11.1-27.8). The most common severe toxicities were neutropenia (38% of patients) and asthenia (11% of patients). CONCLUSION: The combination of biweekly vinorelbine and UFT in patients with metastatic breast cancer pretreated with anthracyclines and taxanes is a well tolerated and effective regimen. AEMPS Trial Registration No.: 00-0534.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Recuperativa/métodos , Tegafur/uso terapéutico , Uracilo/uso terapéutico , Vinblastina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Taxoides/uso terapéutico , Tegafur/administración & dosificación , Tegafur/efectos adversos , Uracilo/administración & dosificación , Uracilo/efectos adversos , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Vinorelbina
15.
Clin Transl Oncol ; 13(1): 61-6, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21239357

RESUMEN

AIM: Advanced pancreatic cancer has a bad prognosis, with a median overall survival (OS) no longer than 4-6 months. Since the end of last century, monotherapy with gemcitabine has remained the elective therapy, but new schedules are needed in order to improve these results. We aim to evaluate the efficacy of tegafur and levofolinic acid (LV) associated with gemcitabine, as well as its toxicity, progression-free survival and OS in advanced pancreatic cancer. PATIENTS AND METHODS: An open-label, multicentric, prospective, non-controlled trial was carried out on patients with advanced or disseminated pancreatic cancer. Gemcitabine 1250 mg/m² was administered on the 1st and 8th days of the cycle, tegafur 750 mg/m²/day for 21 consecutive days and LV 25 mg/day continuously, every 28 days, with a maximum of six cycles. The primary variable was tumour overall response rate (ORR). Secondarily, time to progression (TTP), OS and scheme toxicity were determined. RESULTS: Forty patients were recruited; the male/female ratio was 30:10, with a mean age of 61 years. Forty percent had a Karnofsky index of 90% or 100%. Only 11 patients (27%) completed the six cycles of treatment, but more than 50% received three or more cycles. Dose intensity was 89.56% for gemcitabine and 87.36% for tegafur. Efficacy ORR was 22.5% (CI 95%, 6-37%). TTP was 3.87 months (CI 95%, 2.1-5.6), time to treatment failure was 2.97 months (CI 95%, 2.43-4.67) and OS 6.3 months (CI 95%, 4-7). The chemotherapeutic combination was well accepted; most haematologic and non-haematologic toxicities were grade 1 or 2. The most prevalent grade 3/4 toxicities were asthenia (30%), liver biochemistry disorders (25%), diarrhoea (15%) and stomatitis (12%). CONCLUSIONS: The administration of gemcitabine, associated with oral tegafur and leucovorin, has activity against advanced pancreatic cancer, with an adequate toxicity profile.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Tegafur/administración & dosificación , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Administración Oral , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Análisis de Supervivencia , Tegafur/efectos adversos , Resultado del Tratamiento , Gemcitabina
16.
Clin Transl Oncol ; 9(1): 40-7, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17272229

RESUMEN

PURPOSE: To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy. METHODS: We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m(2) p.o. days 1 to 21, Vinorelbine 25 mg/m(2) i.v. days 1 and 8 and Cisplatin 100 mg/m(2) i.v. day 1 (UFTVP) each 21 days for 4 courses, followed by Radiotherapy concomitant with UFT 100 mg/m(2) p.o. daily and Carboplatin AUC = 0.5 i.v. weekly (RT/UFTJ) in patients (pts) with Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma (IV-B-SCHNC). Primary endpoint was Complete Response to induction UFTVP and secondary endpoints were Disease Free Status Rate after locoregional treatment and long-term Overall Survival. Between 1994 and 1997, 32 pts were included. RESULTS: Complete Response to Induction UFTVP was 59% (95% CI: 48%-70%). Main toxicity of UFTVP was G 3,4 neutropenia (94% of pts; 25% developed febrile neutropenia and 1 of this pts dead). After Induction Chemotherapy with UFTVP, 30 pts received radiotherapy and 25 of them received concomitant Carboplatin and UFT (RT/UFTJ): main toxicity was mucositis (G3-4: 72%) and one patient died during RT/UFTJ because pneumonia. Twenty-five pts (78%) were alive and disease free at the end of the whole treatment. Actuarial 5 year Overall survival is 32%. CONCLUSION: Although toxicity is important, this approach has interesting activity and deserves further investigation.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/terapia , Trasplante de Células Madre de Sangre Periférica , Vinblastina/análogos & derivados , Adulto , Anciano , Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Terapia Combinada , Femenino , Fiebre/inducido químicamente , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Pronóstico , Tasa de Supervivencia , Tegafur/uso terapéutico , Factores de Tiempo , Uracilo/uso terapéutico , Vinblastina/uso terapéutico , Vinorelbina
17.
São Paulo; s.n; 2007. 107 p. ilus, tab.
Tesis en Portugués | LILACS | ID: lil-464473

RESUMEN

O desenvolvimento clínico de novos fármacos é uma tarefa bastante complexa, que requer a participação de um grande número de investigadores e instituições. A disponibilidade de fármacos ativos contra o câncer de cólon e reto avançado sempre foi limitada, e por muitos anos este foi considerado um tumor resistente ao tratamento sistêmico, sendo essencialmente incurável a partir do momento em que se detectavam metástases à distância. Entretanto, a última década testemunhou um notável progresso no tratamento desta doença, graças ao desenvolvimento de diversos novos fármacos. Material e métodos: Revisamos nossa contribuição ao tratamento do câncer de cólon e reto avançado, representada por 94 manuscritos indexados (Pubmed, 06/08/2007), e 82 trabalhos apresentados em congressos internacionais...


Introduction: The clinical development of new drugs is a complex task that requires the participation of a large number of investigators and institutions. The availability of active drugs against advanced colorectal cancer has always been limited, and for many years this was considered a resistant tumor, which was essentially incurable once it had metastasized. However, the last decade has witnessed a remarkable progress in the treatment of this disease, thanks to the development of several new drugs. Material e methods: We reviewed our contribution to the treatment of advanced colorectal cancer through 94 indexed manuscripts (Pubmed, august 06, 2007), and 82 abstracts presented at International Congresses. Of those, we selected 51 publications that best represent our line of research, and our contribution to the treatment of this cancer. Results: We have a total of 10 drugs with proven activity against colorectal cancer. We have contributed in a substantial way for the clinical approval of two of those drugs, the oral capecitabine and the UFT, which can replace the old 5-fluorouracil with some advantages. We have also participated in the clinical development of irinotecan, oxaliplatin, bevacizumab and cetuximabe. Conclusion: We have participated in the development of the majority of new drugs available for the treatment of colorectal cancer. The availability of these new drugs has changed the natural history of this tumor, and patients may now expect not only an increase in median survival, but the presence of distant metastasis is not necessarily an impediment for a treatment with curative intent.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias Colorrectales/tratamiento farmacológico , Administración Oral , Ensayos Clínicos Fase II como Asunto , Tegafur/administración & dosificación , Uracilo/administración & dosificación
18.
São Paulo; s.n; 2007. 107 p. tab.
Tesis en Portugués | Inca | ID: biblio-933537

RESUMEN

Infusões prolongadas de 5-fluorouracil são mais seguras e potencialmente mais efetivas no tratamento do câncer de cólon metastático do que infusões rápidas da mesma medicação. No entanto, infusões prolongadas requerem a disponibilidade de um acesso venoso central, bem como de bombas de infusão dispendiosas. O desenvolvimento de fluoropirimidinas orais permitiu que pacientes fossem expostos ao 5- fluorollracil por longo tempo, com maior conveniência. UFT e leucovorin administrados três vezes ao dia demonstraram previamente uma eficácia equivalente, com menor toxicidade, quando comparados a um regime convencional de infusão rápida de 5- fluorouracil e leucovorin. Este estudo com 98 pacientes foi desenhado e conduzido com objetivo de demonstrar equivalência no tempo de progressão com o uso de UFT e leucovorin administrados duas vezes ao dia, com o uso da mesma combinação administrada três vezes ao dia. Objetivos secundários incluíram análise de toxicidade, resposta objetiva e sobrevida global. O tempo mediano de progressão foi de 3,8 meses, comparado com 3,5 meses observados com o uso da medicação três vezes ao dia e a taxa de resposta foi de 11%, com uma sobrevida mediana de 12,8 meses, sendo comparável aos resultados de 12% e 12,4 meses obtidas com o uso da combinação três vezes ao dia. A incidência de diarréia com graus 3 e 4 foi de 30% no regime de administração duas vezes ao dia, e 21 % no de três vezes ao dia. Esses resultados sugerem que o uso de UFT e leucovorin duas vezes ao dia tem eficácia e toxicidade similares àquelas obtidas com o uso da mesma medicação três vezes ao dia


Prolonged infusions have been shown to be safer and potentially more effective than bolus regimens of 5- fluorouracil as treatment for advanced colorectal cancer. However, infusional 5- fluorouracil requires central venous access and costly infusion pumps. Development of oral fluoropyrimidines has allolled longer exposures to 5-fluorouracil with increased convenience. UFT and leucovorin given thrice daily showed improved safety and no significant difference in survival or response rate compared with bolus 5- fluorouracil and leucovorin. This study with 98 patients was conducted to evaluate whether UFT and leucovorin given twice daily provided comparable time to progression (TTP) to the same combination administered three times a day. Secondary objectives included evaluation of toxicity, overall tumor response rate, and survival. Median time to progression was 3.8 months, compared with 3.5 months observed with the thrice-daily regimen. The twice-daily regimen had a response rate of 11 % and median survival of 12.8 months, comparable to the 12% and 12.4 months seen with the thrice-daily regimen. The incidence of grade 3-4 drugrelated diarrhea was 30% on the twice-daily and 21 % on the thrice-daily schedule. Results suggest that the twice-daily schedule has similar safety and efficacy to the thrice-daily schedule


Asunto(s)
Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Administración Oral , Ensayos Clínicos Fase II como Asunto , Neoplasias Colorrectales/tratamiento farmacológico , Tegafur/administración & dosificación , Uracilo/administración & dosificación
19.
Clin Transl Oncol ; 8(7): 500-7, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16870540

RESUMEN

BACKGROUND AND PURPOSE: To investigate the presence of 5-Fluorouracil (5-FU) in pelvic tissue after oral administration of tegafur. To measure tegafur and 5-FU concentrations in normal rectal mucosa, perirectal fat and residual tumor in rectal cancer patients receiving preoperative chemoradiation. To correlate drug concentrations with cancer downstaging effects. PATIENTS AND METHODS: Three tissue samples taken from 16 surgical specimens after recto-sigmoid resection were analyzed. Tegafur and 5-FU concentrations were measured using high-performance liquid chromatography. 16 patients with locally advanced rectal cancer were treated with preoperative pelvic irradiation (45-50 Gy) sensitized with oral tegafur (400 mg for every 8 hours daily). Seven patients received a precharge dose of tegafur (400 mg oral every 8 hours) 24 hours before surgery. RESULTS: In 8 of the 9 patients who did not receive a precharge dose, detectable levels of tegafur were observed in fat tissue, normal mucosa and tumor, but detectable 5-FU levels were only observed in one patient. Mean concentrations (ranges) for tegafur in fat, normal mucosa and tumor in patients without the precharge dose were 72.19 (12.1-205.6), 179.53 (11.30-727.7) and 252.35 (27.9-874.6) ng/g, respectively; mean concentrations for 5-FU in the same samples were 0.95, 1.92 and 2.68 ng/g (1 patient), respectively. In patients receiving a tegafur precharge, both tegafur and 5-FU were present in all tissue samples with the exception of 2 fat samples, in which drug concentrations were undetectable. 5-FU levels were higher in tumor than other sites, with a median value of 68.24 ng/g (range 3.8-283.05 ng/g). Tegafur levels were also higher in tumor samples than other sites (mean 3446.53 ng/g, range 1044.5-7847.0 ng/g), except in 2 patients who had higher levels of tegafur in normal mucosa. CONCLUSIONS: Tegafur and 5-FU are not always present in pelvic tissues 5 to 6 weeks after oral administration of tegafur. Both drugs were present in the tissues analyzed, in relevant concentrations, 24 hours after oral administration of tegafur. The data obtained suggest a tendency (not significant) toward a correlation between levels of 5-FU present in the residual tumor and cancer downstaging.


Asunto(s)
Antimetabolitos Antineoplásicos/metabolismo , Fluorouracilo/metabolismo , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Tegafur/metabolismo , Tejido Adiposo/metabolismo , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Femenino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Neoplasia Residual/metabolismo , Pelvis , Neoplasias del Recto/metabolismo , Recto/metabolismo , Tegafur/uso terapéutico , Resultado del Tratamiento
20.
Clin Transl Oncol ; 8(6): 423-9, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16790395

RESUMEN

PURPOSE: To assess the quality of life in a group of rectal cancer patients during the treatment period. MATERIAL AND METHODS: A sample of 83 rectal cancer patients in Dukes' stages B2 or C who started a chemoradiotherapy treatment followed by surgery, have filled in the EORTC core questionnaire QLQC30 and the colorectal module QLQ-CR38, in three moments during the treatment and follow-up periods: at the beginning of the treatment, at the end of the chemoradiotherapy, and after surgery. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. RESULTS: Quality of life scores of patients who have followed the treatment has been good in most dimensions, and has shown similar to the clinical data. Soft and moderate alterations have appeared in the areas of disease symptoms, treatment toxicity, fatigue, emotional and sexual functioning, and also in functional areas after surgery. Quality of life has been stable or has had small changes in most dimensions. A worsening in toxicity areas has appeared after the neoadyuvant treatment. After surgery there has been a worsening in functional areas, fatigue and appetite loss, and an improvement in diarrhoea. CONCLUSIONS: Quality of life scores and clinical data indicate that the situation of the patients who have received the treatments has been good. Patients under treatment stood it adequately.


Asunto(s)
Terapia Neoadyuvante , Calidad de Vida , Neoplasias del Recto/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Imagen Corporal , Emociones , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios , Radioterapia/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Conducta Sexual , Tegafur/administración & dosificación , Tegafur/efectos adversos , Trastornos Urinarios/etiología
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