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1.
Clin. transl. oncol. (Print) ; 25(5): 1455-1462, mayo 2023. graf
Artigo em Inglês | IBECS | ID: ibc-219528

RESUMO

Introduction The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. Patients and methods This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. Result 122 patients with a median age of 61 years were included. 89% of patients had PS 0–1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74–6.15 months) and 10.15 (95% CI 7.47–12.82 months), respectively. Disease control rate 59.8%. The most common grade 3–4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58–17.32) in patients with hypertension vs 7.78 (95% CI 5.02–10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. Conclusions Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response (AU)


Assuntos
Humanos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Hipertensão/induzido quimicamente , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem
2.
Clin. transl. oncol. (Print) ; 24(11): 2155-2165, noviembre 2022. graf, tab
Artigo em Inglês | IBECS | ID: ibc-210143

RESUMO

Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB).MethodsIn this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38).ResultsBetween February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B.ConclusionsThe BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation. (AU)


Assuntos
Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , DNA Tumoral Circulante/genética , Neoplasias do Colo/etiologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
3.
Farm. hosp ; 46(4): 224-233, julio 2022. tab
Artigo em Espanhol | IBECS | ID: ibc-210119

RESUMO

Objetivo: El objetivo de la presente revisión sistemática es analizar losdatos publicados sobre la eficacia y seguridad de las dosis superioresa los 180 mg/m2 de irinotecán recomendadas en la ficha técnica enpacientes con cáncer colorrectal metastásico tratados con el esquemaFOLFIRI y con genotipo UGT1A1*1/*1 y *1/*28.Método: Se realizó una revisión sistemática mediante una búsquedabibliográfica en Medline y Embase de los artículos publicados hastadiciembre de 2021. Los métodos utilizados se basaron en los recomendados según Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA). Los criterios para la inclusión de los estudios se definieron previamente en base a los dos objetivos secundarios que abordaesta revisión: 1) Analizar la magnitud de la diferencia de la respuestaclínica y 2) estudiar la magnitud de la diferencia de los efectos adversosa irinotecán a dosis altas, en comparación con las dosis descritas en laficha técnica para el esquema FOLFIRI en pacientes con cáncer colorrectal metastásico con el genotipo UGT1A1*1/*1 o *1/*28.Resultados: La estrategia de búsqueda reportó un total de 98 referencias, de las que 13 fueron seleccionadas para el análisis, 7 (53,8%) evaluando tanto eficacia como seguridad y 6 (46,2%) únicamente seguridad. En relación con los estudios que evaluaron eficacia y seguridad,6 (85,7%) se mostraron favorables al aumento de dosis en términos detasa de respuesta objetiva y supervivencia libre de progresión e, incluso,en 2 de ellos en supervivencia global. Los estudios que evaluaron seguridad apuntan a que dosis de irinotecán superiores a 180 mg/m2 sontoleradas por la mayor parte de los pacientes UGT1A1*1/*1 y *1/*28. (AU)


Objective: The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 ofirinotecan recommended in the drug’s summary of product characteristicsin metastatic colorectal cancer patients with genotypes UGT1A1*1/*1 or*1/*28 who are treated with the FOLFIRI regimen.Method: A systematic review of the literature was carried out in Medlineand Embase searching for articles published up to December 2021. Themethods used were based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.The criteria for the inclusion of studies were previously defined based on thetwo secondary goals addressed in this review: 1) To analyze the magnitudeof the differences in clinical responses and 2) To study the magnitude of thedifferences in adverse effects of irinotecan at high doses, as compared tothe doses described in the summary of product characteristics corresponding to the FOLFIRI regimen in patients with metastatic colorectal cancerwith genotypes UGT1A1*1/* 1 or *1/*28.Results: The search yielded a total of 985 references, of which 13 wereselected for analysis. Seven evaluated both efficacy and safety and six only safety. With regard to the studies that evaluated both efficacy andsafety, six out of seven (85.7%) were in favor of increasing irinotecan doseaccording to the objective response rate and progression-free survival.Two of them even recommended dose increases based on overall survival.Irinotecan safety studies suggest that doses higher than 180 mg/m2 aretolerated by most UGT1A1*1/*1 and *1/*28 patients. (AU)


Assuntos
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/efeitos adversos , Glucuronosiltransferase/genética , Glucuronosiltransferase/uso terapêutico , Genótipo , Irinotecano/efeitos adversos , Leucovorina/efeitos adversos
4.
Clin. transl. oncol. (Print) ; 23(9): 1838-1846, sept. 2021. graf
Artigo em Inglês | IBECS | ID: ibc-222183

RESUMO

Background Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. Methods We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. Results We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02–6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28–16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82–45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30–49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). Conclusions TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Capecitabina/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Fluoruracila/uso terapêutico , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Prognóstico
5.
Clin. transl. oncol. (Print) ; 23(8): 1520-1528, ago. 2021. tab
Artigo em Inglês | IBECS | ID: ibc-222150

RESUMO

Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment (AU)


Assuntos
Humanos , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Fatores Etários
6.
Clin. transl. oncol. (Print) ; 23(4): 812-819, abr. 2021. graf
Artigo em Inglês | IBECS | ID: ibc-220917

RESUMO

Background/objectives The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. Methods This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival—OS) and toxicity. Results A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil–lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. Conclusions In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/secundário , Análise de Sobrevida , Resultado do Tratamento , Estudos Retrospectivos
7.
Arch. Soc. Esp. Oftalmol ; 95(5): 231-235, mayo 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-198613

RESUMO

La intoxicación por ingesta de metanol es una entidad frecuentemente descrita en la literatura, no así la intoxicación vía transdérmica o inhalatoria. Suele cursar con daño multiorgánico variable, entre lo que destaca la afectación visual, neurológica y digestiva, así como las alteraciones metabólicas y electrolíticas que pueden llegar a causar la muerte. El contacto con tolueno por inhalación ocupacional o intencional puede producir también alteraciones neurológicas. En este artículo se expone el caso de una paciente mujer que acude al servicio de urgencias por pérdida visual bilateral secundaria a una intoxicación accidental (inhalatoria-transdérmica) con un disolvente que contenía metanol y tolueno, entre otros compuestos, y que durante el ingreso evoluciona favorablemente tras tratamiento con etanol en perfusión y corticoides


Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favourable outcome during admission after treatment with ethanol in perfusion and corticosteroids


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Metanol/envenenamento , Tolueno/envenenamento , Cegueira/induzido quimicamente , Cegueira/diagnóstico por imagem , Cegueira/tratamento farmacológico , Tomografia Computadorizada por Raios X , Oftalmoscopia , Etanol/uso terapêutico , Leucovorina/uso terapêutico , Antídotos/uso terapêutico , Metilprednisolona/uso terapêutico , Glucocorticoides/uso terapêutico
9.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 46(2): 81-85, abr.-jun. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-183393

RESUMO

El embarazo ectópico cervical representa una forma de gestación extrauterina infrecuente, asociada a una alta tasa de morbimortalidad. Se estima que uno de cada 9000 embarazos ectópicos se implantan a nivel del cérvix (menos del 1% de las gestaciones extrauterinas). Los recientes avances en el diagnóstico por imagen y en la ultrasonografía de alta resolución han hecho posible el diagnóstico precoz y, en consecuencia, mejorar las opciones conservadoras de tratamiento, tanto médicas como quirúrgicas. Entre ellas, la pauta multidosis de tratamiento con metotrexato sistémico puede ser una opción eficaz y segura, con una tasa de éxito del 92,7%, reduciendo considerablemente el número de complicaciones graves y preservando la fertilidad. A continuación, presentamos el caso de una paciente diagnosticada de gestación ectópica cervical, tratada mediante la pauta multidosis de metotrexato intramuscular asociada a ácido folínico, con una excelente respuesta y resolución completa


Cervical pregnancy is a rare form of extra-uterine pregnancy, and is associated with high rate of morbidity and mortality. It is estimated that 1 of 9000 ectopic pregnancies are implanted at the level of the cervix (less than 1% of extra-uterine pregnancies). Recent advances in diagnostic imaging and high resolution ultrasound have made its early diagnosis possible, and consequently, improve the conservative medical and surgical treatment. Among them, the multiple-dose treatment scheme with systemic methotrexate can be an effective and safe option. This has a success rate of 92.7%, with a considerable reduction in the number of major complications, as well as preserving fertility. The case is presented of a patient diagnosed with cervical ectopic pregnancy, treated with a scheme of multiple doses of intramuscular methotrexate combined with folinic acid, with an excellent response and complete resolution


Assuntos
Humanos , Feminino , Gravidez , Adulto , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/tratamento farmacológico , Abortivos não Esteroides/uso terapêutico , Metotrexato/uso terapêutico , Leucovorina/uso terapêutico
11.
Farm. hosp ; 43(2): 56-60, mar.-abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-182591

RESUMO

Objetivo: Evaluar y comparar la calidad de vida de pacientes con cáncer colorrectal no metastásico tratados con el esquema FOLFOX o XELOX. Método: Estudio descriptivo prospectivo de 24 meses de duración (octubre 2015-octubre 2017) en pacientes con cáncer colorrectal no metastásico en tratamiento quimioterápico adyuvante. Se pasó a los pacientes el cuestionario de calidad de vida EORTC QLQ-C30 al inicio del tratamiento y a las 12 semanas. Variables recogidas: exposición (esquema quimioterápico), control (datos demográficos, de la enfermedad y del tratamiento) y respuesta (puntuaciones del cuestionario). El análisis estadístico se efectuó con el programa SPSS(R) 15.0. Resultados: Se incluyeron 30 pacientes, encontrándose diferencias estadísticamente significativas en el ítem rol emocional a las 12 semanas de tratamiento (FOLFOX 92 puntos versus XELOX 82 puntos; p = 0,036). Además, los pacientes tratados con FOLFOX presentaron un empeoramiento clínicamente relevante en actividades cotidianas, estreñimiento e insomnio; mientras que los tratados con XELOX mostraron un empeoramiento clínicamente relevante en actividades cotidianas, estreñimiento, fatiga, náuseas, vómitos, anorexia y diarrea. Conclusiones: Los pacientes tratados con el esquema XELOX se encontraron peor emocionalmente a las 12 semanas del tratamiento adyuvante que los tratados con FOLFOX y presentaron empeoramiento en fatiga, náuseas, vómitos, anorexia y diarrea


Objective: To evaluate and to compare quality of life of patients with non-metastasic colorectal cancer treated either with FOLFOX or with XELOX scheme. Method: Descriptive prospective study during 24 months (October 2015-October 2017) for patients with non-metastasic colorectal cancer in chemotherapy adyuvant treatment. EORTC QLQ-C30 questionnaire was filled by patients at the beginning and at week 12 of adjuvant treatment. Variables collected: exposure (chemotherapeutic scheme administered), control (demographic data, disease data, treatment data) and response (scores obtained from the questionnaire). The data statistical analysis was carried out with the SPSS(R) 15.0 programme. Results: 30 patients were included. Statistically significant differences were found in emotional role item at the middle of the treatment (FOLFOX 92 points vs. XELOX 82 points; p = 0,036). Patients with FOLFOX presented a clinically relevant worsening in terms of daily activities, constipation and insomnia. Patients treated with XELOX a clinically relevant worsening in daily activities, constipation, fatigue, nausea, vomiting, anorexia and diarrhoea were observed. Conclusions: Patients with XELOX scheme referred to have worse emotionally status in the middle of the adjuvant treatment than patients treated with FOLFOX scheme and presented a worsening in items fatigue, nausea, vomiting, anorexia and diarrhoea


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/psicologia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Qualidade de Vida , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
12.
Rev. lab. clín ; 11(2): 64-72, abr.-jun. 2018. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-174357

RESUMO

Introducción. La monitorización terapéutica de metotrexato (MTX) es una práctica indicada en el seguimiento del tratamiento de la leucemia linfoblástica aguda para ajustar las dosis de rescate con leucovorina y evitar toxicidad. El objetivo de nuestro trabajo fue evaluar el desempeño de un método bioanalítico por cromatografía líquida en el control de tratamientos pediátricos de leucemia linfoblástica aguda. Materiales y métodos. Se analizó la evolución de la concentración plasmática del fármaco en 61 pacientes, divididos en 2 grupos según el tipo de tratamiento con MTX: infusión de 24h e infusión de 36h. Alícuotas de 250μL de plasma pretratado se analizaron utilizando un método analítico validado, en un cromatógrafo Agilent 1260 con una columna Zorbax Eclipse XDB-C18 (4,6×150mm, 5μm) y fase móvil compuesta por acetonitrilo y solución reguladora de acetato de sodio 0,05mol/L a pH 3,5. La detección se efectuó a 305nm. Resultados. El método no presentó interferencias por metabolitos ni otros fármacos. El límite inferior de cuantificación fue de 0,05μmol/L, la precisión y la exactitud inter e intraensayo fueron aceptables en el rango (0,05-5,0μmol/L), verificándose un comportamiento lineal. El 29,4% de los pacientes con infusión de 24h y el 60% de aquellos con infusión de 36h presentaron niveles plasmáticos tóxicos de MTX, por lo que debieron adelantarse y/o reforzarse los rescates con leucovorina. Conclusiones. El método cromatográfico resultó eficiente y accesible para la monitorización terapéutica de MTX en pacientes pediátricos, permitiendo la toma de decisiones médicas pertinentes en un corto tiempo de análisis


Introduction. Therapeutic drug monitoring of methotrexate (MTX) is a practice used during acute lymphoblastic leukaemias treatments in order to adjust the leucovorin rescue dose and avoid toxicity. The aim of this work was to evaluate the performance of a bioanalytical method based on liquid chromatography in the control of paediatric acute lymphoblastic leukaemia treatments. Materials and methods. MTX plasma concentrations were evaluated in a total of 61 patients, divided in 2 groups according to the treatment: 24h infusion and 36h infusion. The method used 250μL aliquots of pre-processed plasma, using a validated analytical method, in an Agilent 1260 chromatograph with a 5μm Zorbax Eclipse XDB-C18 column (4.6×150mm) and a mobile phase composed of acetonitrile and 0.05mol/L of a sodium acetate buffer solution at pH 3.5. The detection was performed at 305nm. Results. The method did not show interferences by metabolites or other drugs. The lower limit of quantitation was 0.05μmol/L. Inter- and intra-assay precision and accuracy were acceptable in the working range (0.05-5.0μmol/L), and linear behaviour was observed. Toxic plasma levels of MTX were observed in 29.4% and 60% of the patients from 24h infusion and 36h infusion, respectively. Therefore, leucovorin rescue treatment was either applied earlier or reinforced. Conclusions. The chromatography method was efficient and accessible for the therapeutic drug monitoring of MTX in paediatric patients, allowing appropriate medical decision making within a short time of analysis


Assuntos
Humanos , Criança , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Metotrexato/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Leucovorina/uso terapêutico , Terapia Combinada/métodos , Quimioterapia Combinada/métodos , Monitoramento de Medicamentos/métodos , Estudos Retrospectivos , Formas de Dosagem
13.
Clin. transl. oncol. (Print) ; 18(6): 608-616, jun. 2016. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-152756

RESUMO

Background: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. Methods: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. Results: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10-0.88)] and OS [p < 0.001, HR 0.10 (0.04-0.46)], as were pT stage and TNM stage, respectively. Conclusions: RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer


No disponible


Assuntos
Humanos , Masculino , Feminino , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Prognóstico , Gastrectomia/métodos , Genes ras , Proteínas ras/análise , Quimioterapia Adjuvante , Estudos Retrospectivos , Carcinoma/diagnóstico , Carcinoma/tratamento farmacológico , Quimiorradioterapia/métodos , Quimiorradioterapia , Leucovorina/uso terapêutico , Fluoruracila/uso terapêutico
14.
Clin. transl. oncol. (Print) ; 17(11): 856-861, nov. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-143455

RESUMO

Purpose. In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. Methods. We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m2 iv with leucovorin 200 mg/m2 iv and 1200 mg/m2 in 46-hour infusion of 5-fluorouracil (D’Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m2/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. Results. Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3–102.1 months), and the 3-year survival rates were 52.7 %. Conclusions. This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results (AU)


No disponible


Assuntos
Feminino , Humanos , Masculino , Fluoruracila/uso terapêutico , Quimioterapia Adjuvante , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante , Leucovorina/uso terapêutico , Estômago , Estômago/patologia , Estudos Retrospectivos , 28599 , Estimativa de Kaplan-Meier , Intervalos de Confiança
16.
Clin. transl. oncol. (Print) ; 14(8): 606-612, ago. 2012.
Artigo em Inglês | IBECS | ID: ibc-126957

RESUMO

INTRODUCTION: The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC). MATERIALS AND METHODS: 191 chemotherapy-naïve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3 months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint. RESULTS: 183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6 months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6 weeks, and for body pain and emotional role functioning after 6 and 12 weeks; all of these favored the FOLFOX4 arm (p ≤ 0.05). CONCLUSIONS: TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Quinazolinas/administração & dosagem
17.
Clin. transl. oncol. (Print) ; 14(2): 132-137, feb. 2012.
Artigo em Inglês | IBECS | ID: ibc-126112

RESUMO

INTRODUCTION: The aim of this study is to determine the interobserver variability (IV) between radiation oncologists (RO) in target volume delineation for postoperative gastric cancer (GC) radiotherapy planning. MATERIALS AND METHODS: Four physicians were asked to delimitate clinical target volume (CTV) on the same 3D CT images in 9 postoperative radiochemotherapy GC patients. Instructions were given to include tumour bed, remaining stomach, anastomosis, duodenal loop and local lymph nodes. The principal variable was spatial volume discrepancy between the main observer (called "A") and other observers (all called "B"), which were compared using the mathematical formula A⌣B/A⌢B, applied to the 3D CT images using Boolean operators. Analysis of variance with two random effects (observers and patients) was performed. RESULTS: Mean volumes were 1410 cm(3) for OBA, 1231 cm(3) for OB2, 734.6 cm(3) for OB3 and 1350 cm(3) for OB4. Discrepancies were 519.9±431.6 cm(3) for OB2, 652.1±294.36 cm(3) for OB3 and 225.90±237.07 cm(3) for OB4. Standard deviation ascribed to patients as random effect was 898.6 cm(3) and that ascribed to observers was 198.10 cm(3), considered as a statistically significant difference. CONCLUSIONS: A significant IV in target delineation that can be attributed to many factors depends more on patients' characteristics than RO delineating decisions (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radioterapia (Especialidade)/métodos , Radioterapia (Especialidade)/tendências , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Gástricas , Neoplasias Gástricas/terapia , Quimiorradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/administração & dosagem , Seguimentos , Leucovorina/administração & dosagem , Recidiva Local de Neoplasia , Recidiva Local de Neoplasia/terapia , Estudos Prospectivos , Tomografia Computadorizada por Raios X
18.
Clin. transl. oncol. (Print) ; 13(11): 798-404, nov. 2011. tab
Artigo em Inglês | IBECS | ID: ibc-125940

RESUMO

Adjuvant chemotherapy is the current standard in the management of patients with localised colon cancer (CC) following curative resection. The use of oxaliplatin plus 5 fluorouracil/leucovorin (FOLFOX) or oxaliplatin plus capecitabine-based (XELOX) regimens, both approved in Europe as adjuvant treatment for stage III CC, has improved prognosis in this stage, but questions on their usefulness in high-risk stage II or elderly CC patients and on the role of some prognostic biomarkers are still pending. In April 2010, a consensus meeting on adjuvant CC treatment based on a revision of the most recent literature was held in Spain. The panel considered the use of adjuvant chemotherapy for high-risk stage II CC patients to be justified. Additionally, the more convenient administration of oral fluoropyrimidines vs. IV continuous infusion 5-FU would make XELOX a more suitable alternative for the patient. A more cautious decision should be taken when prescribing oxaliplatin treatment in patients aged ≥70 (AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Neoplasias do Colo/tratamento farmacológico , Guias de Prática Clínica como Assunto , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico
19.
Prog. obstet. ginecol. (Ed. impr.) ; 54(7): 379-382, jul. 2011.
Artigo em Espanhol | IBECS | ID: ibc-89666

RESUMO

Objetivo. Presentar dos casos de gestación ectópica cervical tratados en forma exitosa con metotrexato sistémico. Sujetos y métodos. Dos pacientes (28 y 35 años de edad) portadoras de una gestación ectópica cervical. Intervenciones: Régimen a días alternos de metotrexato 1mg/kg (días 1, 3, 5 y 7) con rescate de leucovorina (días 2, 4, 6 y 8). Punto final (resultado que se midió): éxito del tratamiento conservador de una gestación ectópica cervical. Resultados. Los dos casos de gestación ectópica cervical fueron exitosamente tratados y la capacidad reproductiva preservada. Conclusiones. El tratamiento conservador de la gestación ectópica con metotrexato sistémico es seguro y coste-efectivo (AU)


Objective. To present two cases of cervical ectopic pregnancy successfully treated with systemic methotrexate. Subjects and methods. Two women with a cervical ectopic pregnancy. Interventions: alternative day regime of methotrexate 1mg/kg (days 1,3,5 and 7) with folinic acid rescue (days 2, 4, 6, and 8). End points: successful treatment. Results. Two cases of ectopic cervical pregnancy were successfully treated and preserved their reproductive capability. Conclusions. Conservative medical treatment of cervical ectopic pregnancy with systemic methotrexate is safe and effective (AU)


Assuntos
Humanos , Feminino , Adulto , Gravidez Ectópica/tratamento farmacológico , Metotrexato/uso terapêutico , Leucovorina/uso terapêutico , Metrorragia/complicações , Metrorragia/diagnóstico , Metrorragia/tratamento farmacológico , Ultrassonografia
20.
Clin. transl. oncol. (Print) ; 13(6): 419-425, jun. 2011. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-124682

RESUMO

PURPOSE: FOLFOX (a combination of leucovorin, fluorouracil and oxaliplatin) has achieved substantial success in the treatment of colorectal cancer (CRC) patients. However, about half of all patients show resistance to this regimen and some develop adverse symptoms such as neurotoxicity. In order to select patients who would benefit most from this therapy, we aimed to build a predictor for the response to FOLFOX using microarray gene expression profiles of primary CRC samples. PATIENTS AND METHODS: Forty patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined according to the best observed response at the end of the first-line treatment. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. We identified discriminating genes whose expression differed significantly between responders and nonresponders and then carried out supervised class prediction using the k-nearest-neighbour method. RESULTS: We identified 27 probes that were differentially expressed between responders and nonresponders at significant levels. Based on the expression of these genes, we constructed a FOLFOX response predictor with an overall accuracy of 92.5%. The sensitivity, specificity, positive and negative predictive values were 78.6%, 100%, 100% and 89.7%, respectively. CONCLUSION: The present model suggests the possibility of selecting patients who would benefit from FOLFOX therapy both in the metastatic and the adjuvant setting. To our knowledge, this is the first study to establish a prediction model for the response to FOLFOX chemotherapy based on gene expression by microarray analysis (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/genética , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Metástase Linfática , Compostos Organoplatínicos/administração & dosagem , Taxa de Sobrevida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
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