Search

Capecitabine is a chemotherapy drug widely used in the treatment of metastatic breast cancer. Despite the clinical benefits, adverse events can influence the continuity of therapy. The on/off protocol was designed with the intention of optimizing treatment with capecitabine due to a likely reduction in adverse events. Thus, the aim of the study was to describe the incidence of adverse events during the use of standard and on/off capecitabine protocols. A retrospective cohort study was carried out, in which 221 patients with metastatic breast cancer were analyzed. The sample was divided into groups and subgroups: A - standard; B - on/off; A1 and B1 reduced dose; A2 and B2 full dose. The adverse event with the highest overall incidence (84%) was palmar-plantar erythrodysesthesia syndrome. Most adverse events showed no statistically significant variation in incidence between groups A and B. A higher incidence of adverse events was observed in patients who underwent full dose in both protocols. Regarding severity, most were classified as grade 1 and there was no statistical difference between groups A and B. The study suggests that switching from standard protocol to on/off, with the aim of reducing the incidence and severity of adverse events, does not have a significant impact. Dose reduction is a viable alternative to decrease the incidence of adverse reactions and is clinically relevant in some cases. La capecitabina es un fármaco de quimioterapia ampliamente utilizado en el tratamiento del cáncer de mama metastásico. A pesar de los beneficios clínicos, los eventos adversos pueden influir en la continuidad de la terapia. El protocolo on/off se diseñó con la intención de optimizar el tratamiento con capecitabina debido a una probable reducción de los eventos adversos. Por lo tanto, el objetivo del estudio fue describir la incidencia de eventos adversos durante el uso de protocolos estándar y on/off de capecitabina. Se realizó un estudio de cohortes retrospectivo, en el que se analizaron 221 pacientes con cáncer de mama metastásico. La muestra fue dividida en grupos y subgrupos: A - estándar; B - encendido/apagado; A1 y B1 dosis reducida; A2 y B2 dosis completa. El evento adverso con mayor incidencia global (84%) fue el síndrome de eritrodisestesia palmar-plantar. La mayoría de los eventos adversos no mostraron una variación estadísticamente significativa en la incidencia entre los grupos A y B. Se observó una mayor incidencia de eventos adversos en los pacientes que recibieron la dosis completa en ambos protocolos. En cuanto a la gravedad, la mayoría se clasificó como grado 1 y no hubo diferencia estadística entre los grupos A y B. El estudio sugiere que el cambio del protocolo estándar a on/off, con el objetivo de reducir la incidencia y la gravedad de los eventos adversos, no tiene un impacto significativo. La reducción de dosis es una alternativa viable para disminuir la incidencia de reacciones adversas y es clínicamente relevante en algunos casos. A capecitabina é um quimioterápico amplamente utilizado no tratamento do câncer de mama metastático. Apesar dos benefícios clínicos, eventos adversos podem influenciar a continuidade da terapia. O protocolo on/off foi desenhado com a intenção de otimizar o tratamento com capecitabina devido a uma provável redução de eventos adversos. Com isso, o objetivo do estudo foi descrever a incidência dos eventos adversos durante uso dos protocolos padrão e on/off de capecitabina. Realizou-se um estudo de coorte retrospectivo, onde foram analisadas 221 pacientes com câncer de mama metastático. A amostra foi dividida em grupos e subgrupos: A - padrão; B - on/off; A1 e B1 dose reduzida; A2 e B2 dose plena. O evento adverso de maior incidência geral (84%) foi a síndrome de eritrodisestesia palmar-plantar. A maioria dos eventos adversos não apresentou variação estatisticamente significativa em relação à incidência entre os grupos A e B. Foi observado maior incidência de eventos adversos nos pacientes que realizaram dose plena em ambos os protocolos. Acerca da gravidade, a maioria foi classificada como grau 1 e não houve diferença estatística entre os grupos A e B. O estudo sugere que a troca de protocolo padrão para o on/off, com o objetivo de reduzir incidência e gravidade dos eventos adversos, não apresenta impacto significativo. Redução da dose é uma alternativa viável para diminuir a incidência de reações adversas sendo clinicamente relevante em alguns casos.

Cancer is the main public health problem in the world. Anticancer drugs can have serious adverse reactions, many of which are potentially fatal if not properly managed. Capecitabine is a chemotherapeutic prodrug that is frequently used in the treatment of breast, colon and rectal cancer. Among the most frequent toxicities in patients undergoing capecitabine use is hand-foot syndrome (HFS). The objective this study was to develop a folder of guidelines for the prevention and treatment of HFS aimed at patients who use capecitabine in order to optimize their treatment. This is an experience report that involved three steps: problem identification; narrative literature review, layout development, illustrations and writing in folder format. The material consisted of simple guidelines, demonstrating the main signs and symptoms of HFS, in addition to a telephone number for contacting the service. Questions related to changing lifestyle habits were also included, such as improving water intake, wearing comfortable shoes and the temperature of the bath water, as well as care with the handling of cleaning products. In addition, non-pharmacological methods were mentioned, such as the use of urea-based creams, aloe vera and laser therapy. We concluded that the elaboration of the folder proposed a printed educational material that allowed a more assertive approach, aimed at the individual, clarifying their doubts and ensuring better treatment. El cáncer es el principal problema de salud pública del mundo. Los medicamentos contra el cáncer pueden tener reacciones adversas graves, muchas de las cuales son potencialmente fatales si no se manejan adecuadamente. La capecitabina es un profármaco quimioterapéutico que se utiliza con frecuencia en el tratamiento del cáncer de mama, colon y recto. Entre las toxicidades más frecuentes en pacientes sometidos a uso de capecitabina se encuentra el síndrome mano-pie (SMP). El objetivo de este estudio fue desarrollar una carpeta de guías para la prevención y el tratamiento del SPM dirigida a pacientes que usan capecitabina con el fin de optimizar su tratamiento. Este es un informe de experiencia que involucró tres pasos: identificación del problema; revisión de literatura narrativa, desarrollo de maquetación, ilustraciones y redacción en formato de carpeta. El material constaba de pautas sencillas, que demostraban los principales signos y síntomas del SMP, además de un número de teléfono para contactar con el servicio. También se incluyeron cuestiones relacionadas con el cambio de hábitos de vida, como la mejora de la ingesta de agua, el uso de zapatos cómodos y la temperatura del agua del baño, así como el cuidado con el manejo de los productos de limpieza. Además, se mencionaron métodos no farmacológicos, como el uso de cremas a base de urea, aloe vera y terapia con láser. Concluimos que la elaboración de la carpeta proponía un material educativo impreso que permitía un abordaje más asertivo, dirigido al individuo, aclarando sus dudas y asegurando un mejor trato. O câncer é o principal problema de saúde pública no mundo. Os fármacos antineoplásicos podem apresentar graves reações adversas, muitas delas são potencialmente fatais se não forem manejadas adequadamente. A capecitabina é um pró-fármaco quimioterápico sendo frequentemente utilizada no tratamento do câncer de mama, cólon e reto. Dentre as toxicidades mais frequentes em pacientes submetidos ao uso de capecitabina está a síndrome mão-pé (SMP). O objetivo deste trabalho foi elaborar um folder de orientações para prevenção e tratamento da SMP direcionado aos pacientes que usam a capecitabina visando à otimização do seu tratamento. Trata-se de relato de experiência que envolveu três etapas: identificação do problema; revisão narrativa da literatura, desenvolvimento do layout, ilustrações e escrita em formato de folder. O material constou de orientações simples, demonstrando quais os principais sinais e sintomas da SMP, além de um telefone para contato com o serviço. Foram inseridas também, questões relacionadas a mudança de hábitos de vida como melhora da ingestão hídrica, uso de sapatos confortáveis e a temperatura da água do banho, além de cuidados com a manipulação de produtos de limpeza. Além disso, foram citados os métodos não farmacológicos como uso de cremes à base de uréia, aloe vera e laserterapia. Concluímos que a elaboração do folder propôs um material educativo impresso que possibilitou abordagem mais assertiva, direcionada ao indivíduo, esclarecendo suas dúvidas e assegurando um melhor tratamento.

BACKGROUND Many transanal platforms have been developed to address the challenge of reach and vision when operating transanally. The single-port robot was specifically designed for narrow-aperture surgery and is a promising platform for minimally invasive transanal surgery. OBJECTIVE The purpose of this phase II trial is to evaluate the safety and feasibility of the initial clinical experience with single-port robot transanal minimally invasive surgery. DESIGN In a prospective phase II trial, patients with rectal neoplasms eligible for local excision were enrolled for single-port robotic transanal minimally invasive surgery. SETTING The study was conducted between October 2018 and March 2020 at a tertiary referral hospital. PATIENTS/INTERVENTION Twenty-six consecutive patients underwent single-port robotic transanal minimally invasive surgery resection of rectal lesions. MAIN OUTCOME MEASURES The primary end point of the study was the efficacy and safety of single-port robotic transanal minimally invasive surgery. RESULTS There were 13 men and 13 women, with an average lesion size of 2.9 cm (range, 1.0-6.0 cm) and average level of 4.8 cm from the anorectal ring (range, 0-30 cm). Ten patients had a preoperative diagnosis of adenocarcinoma, 7 of whom received neoadjuvant chemoradiation (range, 4500-5580 cGy with concurrent oral capecitabine). Eighty-eight percent of cases were completed by single-port robotic transanal minimally invasive surgery; 2 were converted to transanal endoscopic microsurgery, and 1 patient underwent a low anterior resection. There were no piecemeal extractions, and all margins were negative on final pathology. There were no mortalities, and the morbidity rate was 15.4%. There have been no local recurrences, with a mean follow-up of 5.8 months (range, 0-15.9 months). LIMITATIONS The study was limited by small sample size, short-term follow up, and a single-surgeon experience. CONCLUSION Single-port robotic transanal minimally invasive surgery procedures are safe and feasible in patients with select benign and malignant rectal lesions. Future trials will need to evaluate the long-term safety and efficacy of single-port robotic transanal minimally invasive surgery. See Video Abstract at http://links.lww.com/DCR/B605. PRIMERA EXPERIENCIA CLNICA CON CIRUGA MNIMAMENTE INVASIVA TRANSANAL ROBTICA DE PUERTO NICO ENSAYO DE FASE II DE LOS CASOS INICIALES ANTECEDENTES:Se han desarrollado muchas plataformas transanales para abordar el desafio del alcance y la vision cuando se opera de manera transanal. El robot de un solo puerto fue disenado especificamente para la cirugia de apertura estrecha y es una plataforma prometedora para la cirugia transanal minimamente invasiva.OBJETIVO:El proposito de este ensayo de fase II es evaluar la seguridad y viabilidad de la experiencia clinica inicial con la cirugia minimamente invasiva transanal con robot de puerto unico.DISENO:En un ensayo prospectivo de fase II, los pacientes con neoplasias rectales elegibles para la escision local se inscribieron para la cirugia minimamente invasiva transanal robotica de puerto unico.AJUSTE:El estudio se realizo entre octubre de 2018 y marzo de 2020 en un hospital de referencia terciario.PACIENTES / INTERVENCION:Veintiseis pacientes consecutivos fueron sometidos a cirugia minimamente invasiva transanal robotica de puerto unico para reseccion de lesiones rectales.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoracion principal del estudio fue la eficacia y seguridad de la cirugia minimamente invasiva transanal robotica de puerto unico.RESULTADOS:Hubo 13 hombres y 13 mujeres, con un tamano de lesion promedio de 2.9 cm (rango 1.0-6.0 cm) y un nivel promedio de 4.8 cm del anillo anorrectal (rango 0-30 cm). Diez pacientes tenian un diagnostico preoperatorio de adenocarcinoma, 7 de los cuales recibieron quimiorradiacion neoadyuvante (rango 4500-5580 cGy con capecitabina oral concurrente). El 88% de los casos se completaron mediante cirugia minimamente invasiva transanal robotica de puerto unico; 2 se convirtieron a microcirugia endoscopica transanal y 1 se sometio a una reseccion anterior baja. No hubo extracciones parciales y todos los margenes fueron negativos en la patologia final. No hubo mortalidad y una tasa de morbilidad del 15,4%. No ha habido recidivas locales, con un seguimiento medio de 5,8 meses (rango 0-15,9 meses).LIMITACIONES:El estudio estuvo limitado por un tamano de muestra pequeno, un seguimiento a corto plazo y la experiencia de un solo cirujano.CONCLUSION:Los procedimientos de cirugia minimamente invasiva transanal robotica de puerto unico son seguros y factibles en pacientes con lesiones rectales benignas y malignas seleccionadas. Los ensayos futuros deberan evaluar la seguridad y eficacia a largo plazo de la cirugia minimamente invasiva transanal robotica de puerto unico. Consulte Video Resumen en http://links.lww.com/DCR/B605. (Traduccion-Dr. Eduardo Londono-Schimmer).

Introduction: Palmoplantar erythrodysesthesia, also known as hand-foot syndrome (PMS), is an adverse reaction caused by the oral antineoplastic therapy Capecitabine that causes the greatest impact on the quality of life of patients with this chemotherapy treatment. The professional nurse has the nursing consultation as an instrument of care, which enables a systematic and permanent educational intervention fundamental to the composition of individualized and comprehensive care. General Objective: Analyze the actions developed by nurses in the outpatient prevention and treatment of Hand-Foot Syndrome induced by the use of Capecitabine. Methodology: Descriptive study, with a qualitative approach and participant observation, carried out in a reference institute in oncology, located in the State of Rio de Janeiro, from October to November 2020. A field diary was prepared based on data referring to the actions taken by the professional during the nursing consultation, the flow of patients seen in this clinic, the nurse's notes in the patient record book, and the researcher's impressions. Results: After careful analysis of the data, two categories of analysis emerged: administrative actions and technical and educational actions. Conclusion: It was found that the flow followed provides an opportunity for the follow-up of patients using Capecitabine oral antineoplastic in almost its entirety. Nursing consultations are carried out with the preventive intention of establishing the syndrome in an important process of interaction / integration with the patient, using health education as a care strategy for the prevention and management of the syndrome, contributing to the dissemination of knowledge about the nurses' work process in a specialized and contemporary outpatient clinic. Introducción: La eritrodisestesia palmoplantar, conocida popularmente como síndrome mano-pie (SPM), es un efecto adverso provocado por la terapia antineoplásica oral Capecitabina que provoca un mayor impacto en la calidad de vida de estos pacientes. El enfermero profesional tiene la consulta de enfermería como un instrumento asistencial que permite una intervención educativa sistemática, fundamental para la composición de la atención individualizada e integral. Objetivo: Analizar las acciones desarrolladas por enfermeras en la prevención y tratamiento ambulatorio del Síndrome Mano-Pie inducido por el uso de Capecitabina. Metodología: Estudio descriptivo, con abordaje cualitativo y observación participante, realizado en un instituto de referencia en oncología, ubicado en el Estado de Rio de Janeiro, de octubre a noviembre de 2020. Se elaboró ​​un diario de campo a partir de los datos relacionados con las acciones desarrolladas por el profesional durante la consulta de enfermería, el flujo cubierto por los pacientes atendidos en esta clínica, las notas de la enfermera en el libro de registro del paciente y las impresiones del investigador. Resultados: Después de un análisis cuidadoso de los datos, surgieron dos categorías de análisis: acciones administrativas y acciones técnicas y educativas. Conclusión: Se encontró que el flujo seguido brinda una oportunidad para el seguimiento de los pacientes que utilizan el antineoplásico oral Capecitabina en casi su totalidad. Las consultas de enfermería se realizan con la intención preventiva de establecer el síndrome en un importante proceso de interacción / integración con el paciente, utilizando la educación en salud como estrategia asistencial para la prevención y manejo del síndrome, contribuyendo a la difusión del conocimiento sobre las enfermeras. 'proceso de trabajo en una clínica ambulatoria especializada y contemporánea. Introdução: A eritrodisestesia palmo-plantar, também conhecida como Síndrome Mão-Pé (SMP), é uma reação adversa causada pela terapia antineoplásica oral Capecitabina que causa impacto na qualidade de vida dos pacientes com esse tratamento quimioterápico. O profissional enfermeiro tem como instrumento de cuidado a consulta de enfermagem que possibilita uma intervenção educativa sistematizada, fundamental para composição de um cuidado individualizado e integral. Objetivo: Analisar as ações desenvolvidas pelo enfermeiro no ambulatório de prevenção e tratamento da Síndrome Mão-Pé induzida pelo uso de Capecitabina. Metodologia: Estudo descritivo, com abordagem qualitativa e observação participante, realizado em um instituto de referência em oncologia, situado no Estado do Rio de Janeiro, no período de outubro a novembro de 2020. Foi elaborado um diário de campo a partir dos dados referentes às ações desenvolvidas pelo profissional durante a consulta de enfermagem, o fluxo percorrido pelos pacientes atendidos nesse ambulatório, as anotações do enfermeiro no livro de registro dos pacientes e impressões da pesquisadora. Resultados: Após a análise criteriosa dos dados emergiram duas categorias de análise: ações administrativas e ações técnicas e educativas. Conclusão: Identificou-se que o fluxo seguido oportuniza o acompanhamento dos pacientes em uso de antineoplásico oral Capecitabina em sua quase totalidade. As consultas de enfermagem são operacionalizadas com intuito preventivo da instauração da síndrome em um importante processo de interação/integração com o paciente, utilizando-se a educação em saúde como estratégia de cuidado para prevenção e manejo da síndrome, contribuindo para disseminação de conhecimento acerca do processo de trabalho do enfermeiro em ambulatório especializado e contemporâneo.

Objetivo: Analisar o glicogênio muscular, o perfil hematológico e as alterações eletrocardiográficas de ratos tratados com o medicamento a base de capecitabina. Metodologia: Foram utilizados ratos da linhagem Wistar, com 3 a 4 meses de idade e peso de 180 a 200 gramas da ANILAB®, sem restrição alimentar, com temperatura constante de 23 ± 2ºC e ciclo normal de dia e noite, com 12 horas. O medicamento foi administrado por gavagem em uma dose de 359mg/kg, dissolvida em tampão de citrato 40mM, contendo 5% de goma arábica como transporte. Resultados: Foi obsrvado que ocorreu diferença entre os grupos experimentais, sendo que os animais tratados com capecitabina tiverem concentrações menores de glicogênio hepático e muscular, além do medicamento diminuir os parâmetros hematológicos, resultando em alterações eletrocardiográficas importantes. Conclusão: O medicamento modifica a homeostasia metabólica tecidual e altera a reatividade cardiovascular tanto no padrão adrenérgico quanto colinérgico.

Objetivo: Conduzir uma avaliação farmacoeconômica entre XELOX e mFOLFOX6 no tratamento adjuvante e metastático do câncer colorretal, na perspectiva de um hospital de ressarcimento público. Métodos: A análise de custo minimização foi conduzida para pacientes que iniciaram o tratamento nos anos de 2013 e 2014. Técnica de microcusteio foi utilizada para verificar gastos com medicamentos, materiais, exames laboratoriais e de imagem, atendimento ambulatorial e diária de internação, recursos humanos e administrativos e determinar o custo individual de cada alternativa, por paciente. Para avaliar a robustez da análise econômica, foi realizada análise de sensibilidade multivariada em seis diferentes cenários. Resultados: Custo médio para XELOX foi de USD$ 4.637,14 na adjuvância e USD$ 3.831,48 para tratamento paliativo, e um custo para mFOLFOX6 de USD$ 5.474,89 na adjuvância e USD$ 4.432,95 no tratamento paliativo. A análise de sensibilidade manteve a dominância de XELOX. Os custos de materiais e medicamentos representaram cerca de 85% do custo total de XELOX; para mFOLFOX6 esse custo foi em torno de 36%. Já os custos com internação e colocação de cateter ocorreram exclusivamente para mFOLFOX6, que também apresentou maior custo com recursos humanos. Conclusão: Da perspectiva do hospital, XELOX mostrou-se a alternativa menos custosa no tratamento do câncer colorretal. Objective: To conduct a pharmacoeconomic evaluation between XELOX and mFOLFOX6 in the adjuvant and metastatic treatment of colorectal cancer from the perspective of a public reimbursement hospital. Methods: The cost minimization analysis was conducted for patients who started treatment in 2013 and 2014. The micro-costing technique was used to verify expenditures on drugs, materials, laboratory and imaging tests, ambulatory and daily hospitalization, human and administrative resources and determine the individual cost of each alternative, per patient. To evaluate the robustness of the economic analysis, multivariate sensitivity analysis was performed in six different scenarios. Results: There was an average cost for XELOX of U$ 4,637.14 in adjuvant and U$ 3,831.48 for palliative treatment, and a cost for mFOLFOX6 of U$ 5,474.89 in adjuvant and U$ 4,432.95 in palliative treatment. Sensitivity analysis maintained the dominance of XELOX. Material and drug costs accounted for about 85% of the total cost of XELOX; for mFOLFOX6 this cost was around 36%. On the other hand, the cost of hospitalization and placement of a catheter occured exclusively for mFOLFOX6, which also presented a higher cost with human resources. Conclusion: From the perspective of the hospital, XELOX proved to be the least costly alternative on the treatment of colorectal cancer.

Introdução: O uso de antineoplásicos tem sido uma das melhores escolhas de tratamento para o câncer. A capecitabina uma droga utilizada em pacientes com cânceres já metastáticos, tem induzido á reações adversas dermatológica como a SMP (síndrome mão pé). Objetivo: Relatar uma experiência vivenciada numa paciente na unidade de internação de um hospital particular do estado de São Paulo, mostrando a importância de novas pesquisas e novas publicações a respeito de como conduzir e proporcionar qualidade de vida para pacientes em situações semelhantes. Método: Relato de experiência sobre a síndrome mão pé em uma paciente internada na unidade de internação de hospital privado do estado de São Paulo, referenciando os cuidados adequados, e as possíveis condutas. Resultados: Percebe-se a importância da síndrome mão pé (SMP), para a qualidade de vida de pacientes oncológicos em uso de linhas de tratamento que utiliza antineoplásicos com dose acumulativa que pode causar sintomas iniciais, é necessário um olhar diferenciado para não agravar ao nível de comprometer atividade de vida diária do paciente. Conclusão: Através desse relato podemos analisar o tão quanto os ensaios clínicos, novos relatos de experiência e novas comprovações cientificas estão em falta, qual se relaciona a SMP, existe pouca comprovações cientificas a respeito do tema.

Resumen Los tumores neuroendocrinos pancreáticos (TNEsP) son un grupo poco frecuente de neoplasias, pueden ser funcionales y causan síndromes clínicos diversos, o no funcionales, con síntomas secundarios a invasión a estructuras cercanas o enfermedad metastásica (1). Se presenta el caso de una paciente de 55 años con insulinoma maligno con compromiso metastásico extenso, no candidata a intervención quirúrgica, hipoglucemia de difícil manejo sin respuesta a tratamiento con diazóxido y prednisolona, y que requirió manejo con quimioterapia y embolización de metástasis hepáticas, con posterior mejoría clínica, estabilidad de la enfermedad por imágenes diagnósticas y retiro de medicamentos para manejo de hipoglucemia. En seguimiento presenta síntomas de hiperglucemia con HbA1c en 12%, con lo cual se diagnosticó diabetes mellitus de novo y se inició manejo con insulina. Abstract Pancreatic neuroendocrine tumors (TNEP) are a rare group of neoplasms, which can secrete peptide hormones causing various clinical syndromes, or be non-secretory, with symptoms secondary to invasion of neighboring or distant structures (1). The case of a 55-year-old patient with malignant insulinoma with extensive metastatic involvement, not operable, with persistent hypoglycemia refractory to treatment with diazoxide and prednisolone, who received management with chemotherapy and embolization of liver metastases, achieving the withdrawal of medications for the management of hypoglycemia and a tumor response of stable disease in the comparison of images during the 12-month follow-up. During the 15th cycle of chemotherapy, he presented symptoms of hyperglycemia with HbA1c in 12%, with which diabetes de novo mellitus was diagnosed and insulin management was initiated.

La quimioterapia metronómica es un tipo de quimioterapia cuya toxicidad es mínima. Consiste en administraragentes antineoplásicos habituales a intervalos muy próximos uno del otro y a dosis relativamente bajasdurante un tiempo prolongado y sin periodos de descanso farmacológico. Esta terapia reduce la toxicidady elimina la necesidad de tratamientos de soporte, por lo tanto, el empleo de esta modalidad de tratamientoen pacientes con enfermedad metastásica resulta de gran interés. Muchas investigaciones han evaluado laadministración de medicamentos antineoplásicos en esquemas metronómicos, tanto en monoterapia comoen combinación. Los fármacos mayormente estudiados son la ciclofosfamida, vinorelbina y capecitabina.Diversos estudios han mostrado la eficacia y tolerancia de esta terapia combinada con la hormonoterapiae inmunoterapia. Es necesaria mayor evidencia científica para definir cuestiones como: pacientes que másbeneficio puedan obtener y las combinaciones terapéuticas a emplear de acuerdo al tipo de paciente., Metronomic chemotherapy is a type of chemotherapy whose toxicity is minimal. It consists of administeringusual antineoplastic agents at intervals very close to each other and at relatively low doses for a prolonged timewithout periods of pharmacological rest. This therapy reduce toxicity and eliminates the need for supportivetreatments, therefore, the use of this treatment modality in patients with metastatic disease is of great interest.Many investigations have evaluated the administration of antineoplastic drugs in metronomic schemes,both in monotherapy and in combination. The most studied drugs are cyclophosphamide, vinorelbine andcapecitabine. Several studies have shown the efficacy and tolerance of this therapy combined with hormonetherapy and immunotherapy. More scientific evidence is needed to define issues such as: patients who canobtain more benefit and the therapeutic combinations to be used according to the type of patients.

We report the case of a patient with a stage IV ab initio HR-/HER2 positive breast cancer. The patient, treated with pertuzumab and trastuzumab for approximately 8 months, developed a progression of both systemic and cerebral disease. Subsequent treatment with T-DM1 obtained disease control for about 10 months. Afterwards we suggested a therapy based on lapatinib and capecitabine with a clear lasting response at encephalic level. This clinical case suggests that the combination of lapatinib + capecitabine is a valid option in case of double-block progression of HER2 and T-DM1. The interesting activity of lapatinib at encephalic level indicates the drug as one of the best therapeutic options available today in this patient setting (Oncology)

Objective To analyze adverse reactions in patients with nonmetastatic colorectal cancer due to treatment with either innovative or generic capecitabine and/or to the chemotherapeutic regimen employed, to the capecitabine alone, or in combination with oxaliplatin (XELOX). Method Descriptive retrospective study carried out in a secondary level hospital in two study periods (November 2013 -April 2014 and August 2016-May 2017). The collected variables were: exposure (chemotherapy scheme and/or received medication), control (demographics, disease and treatment data), and response (adverse reactions). The statistical analysis of data was performed with the SPSS® 15.0 program. Results Fifty patients were included. According to the administered chemotherapeutic scheme, statistically significant differences were found in the appearance of palmar-plantar erythrodysesthesia, which is more frequent with monotherapy (p < 0.05), and neurotoxicity, thrombocytopenia and neutropenia, which is more frequent with XELOX (p < 0.05). Concerning the capecitabine drug administered, no statistically significant differences were found in the studied adverse reactions. Conclusions The safety profile of two capecitabine formulations -innovative and generic- appears to be associated with the chemotherapy scheme employed, and not the drug itself. Most palmar-plantar erythrody-sesthesia for monotherapy is likely due to the higher dose of capecitabine used in said scheme. The increase in neurotoxicity, thrombocytopenia and neutropenia for XELOX is probably due to cumulative toxicity of two anti-neoplastic drugs. Resumen Objetivo Analizar las reacciones adversas en pacientes con cáncer colorrectal no metastásico debidas al tratamiento con capecitabina innovadora o genérica, y/o al régimen quimioterápico empleado, capecitabina en monoterapia o en combinación con oxaliplatino (XELOX). Método Estudio descriptivo retrospectivo llevado a cabo en un hospital de segundo nivel en dos periodos de estudio (noviembre de 2013-abril de 2014 y agosto de 2016 -mayo de 2017). Las variables recogidas fueron variables de exposición (esquema quimioterápico y/o medicamento recibido), variables de control (datos demográficos, de enfermedad y de tratamiento) y variables de respuesta (reacciones adversas). El análisis estadístico de los datos se efectuó con el programa SPSS® 15.0. Resultados Se incluyeron 50 pacientes. Según el esquema quimioterápico administrado, se encontraron diferencias estadísticamente significativas en la aparición de eritrodisestesia palmo-plantar, más frecuente con monoterapia (p < 0,05), y neurotoxicidad, trombopenia y neutropenia, más frecuentes con XELOX (p < 0,05). Según el medicamento de capecitabina administrado, no se observaron diferencias estadísticamente significativas en las reacciones adversas estudiadas. Conclusiones El perfil de seguridad de dos formulaciones de capecitabina, innovadora y genérica, parece estar asociado al esquema quimioterápico empleado, y no al medicamento en cuestión. La mayor eritro-disestesia palmo-plantar para monoterapia se debe probablemente a la mayor dosis de capecitabina empleada en dicho esquema, y la mayor neurotoxicidad, trombopenia y neutropenia para XELOX se debe probablemente a la toxicidad acumulada de dos fármacos antineoplásicos.

Capecitabine is a prodrug used primarily as a chemotherapeutic agent. Despite its good tolerance, it has several adverse effects, including the appearance of eruptive nevi. We present the case of a patient, with a history of EC IV breast adenocarcinoma and superficial extension melanoma, which developed 2 weeks after the start of therapy with capecitabine multiple eruptive palmoplantar pigmented lesions, with diverse benign dermatoscopic patterns. With the increasing incidence of solid tumors, these agents are being more used. It is important that the treating physician knows its adverse effects and apply non-invasive diagnostic tools like dermoscopy to avoid unnecessary biopsies.

espanolLas complicaciones cardiovasculares son efectos probables de la quimioterapia y pueden abarcar distintas manifestaciones. Para advertir del riesgo del uso de farmacos citotoxicos y de sus efectos adversos cardiovasculares, describimos el caso de una paciente que fue tratada con CPT 11 (irinotecan), capecitabina y bevacizumab, por un adenocarcinoma de colon en estadio avanzado y que desarrollo un sindrome coronario agudo sin elevacion del segmento ST. Consideramos como agente causal mas probable la capecitabina, que es un agente quimioterapico oral empleado como tratamiento de primera linea en el cancer de colon metastasico y de segunda linea en el cancer de mama. Son conocidos sus efectos adversos gastrointestinales, dermatologicos y sobre la medula osea; sin embargo, menos frecuente es la toxicidad cardiologica. EnglishCardiovascular toxicity is a potential complication of anticancer therapies and may include a wide range of manifestations. In order to create awareness of the risk of cytotoxic drugs use and their cardiac side-effects, we report the case of a patient who received treatment with CPT- 11 (irinotecan), capecitabine and bevacizumab due to an advanced- stage colon adenocarcinoma, who developed an acute coronary syndrome without ST elevation. We consider capecitabine as the most plausible inducement of this event, which is an oral chemotherapeutic drug used as first-line treatment in metastatic colon cancer and second-line in breast cancer. Gastrointestinal, cutaneous and hematological are established side effects of capecitabine. Cardiac toxicity is uncommon, even though its range of occurrence is increasing due to the ageing population.

Orientador: Patricia Moriel Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: O câncer colorretal configura-se como a terceira neoplasia mais prevalente no mundo à frente do câncer gástrico, que se encontra na quinta posição. Entre as opções terapêuticas disponíveis para estas neoplasias, destaca-se a capecitabina, que pode ser prescrita combinada ou não a outros quimioterápicos. Trata-se de um antineoplásico oral que, apesar de sua alta eficácia, possui importantes toxicidades associadas ao seu uso, inclusive podendo ser dose-limitantes com impacto significativo na qualidade de vida dos pacientes. O objetivo deste estudo foi avaliar a incidência das principais toxicidades em pacientes em uso de capecitabina para o tratamento de neoplasias gástricas e colorretais e correlacioná-las com a presença de variantes nos genes DPYD e MTHFR, que estão envolvidos em etapas importantes do mecanismo de ação deste quimioterápico. Trata-se de um estudo analítico, observacional do tipo coorte. Foram avaliadas as toxicidades gastrointestinais, hematológicas, renais, dermatológicas, neurológicas, hepáticas e fadiga. A gravidade destes eventos foi classificada pelo Common Toxicity Criteria for Adverse Events (versão 4.0). Também foi avaliada a qualidade de vida do paciente antes do início da quimioterapia e após terceiro ciclo de tratamento através dos questionários geral e específicos para o tipo de neoplasia apresentada desenvolvidos pela European Organisation for Research and Treatment of Cancer e validados para língua portuguesa. A adesão ao tratamento e conhecimento da terapia foram avaliados através das ferramentas Morisky-Green e MedTake. Os pacientes foram genotipados para as seguintes variantes genéticas através da técnica de PCR em tempo real: DPYD*5 (1627A>G), DPYD*9A (85T>C), MTHFR 677C>T e MTHFR 1298A>C. Foram incluídos 109 pacientes (58,61±10,74 anos, 51,38% do sexo masculino) e as toxicidades mais frequentes foram náusea entre as de ordem gastrointestinal, anemia entre as de ordem hematológica, síndrome mão-pé entre as de ordem dermatológica, parestesia entre as de ordem neurológica e fadiga. Com relação à qualidade de vida geral, houve melhora significativa nos domínios "função social" e "dor" após o terceiro ciclo de tratamento. A maioria dos pacientes apresentou alta adesão à capecitabina e o grau de conhecimento em relação ao tratamento por parte dos pacientes melhorou de forma significativa ao longo dos três primeiros ciclos de tratamento. A variante DPYD*5 foi correlacionada com aumento de creatinina não clinicamente significativo e menor incidência de disgeusia entre os pacientes, DPYD*9A com diminuição de hemoglobina sérica não clinicamente significativo e maior incidência de diarreia e MTHFR 677C>T foi associado à linfopenia entre os pacientes participantes do estudo. Mais estudos precisam ser conduzidos em um grupo maior de pacientes para melhor avaliação do potencial destas variantes genéticas no rastreamento prévio ao tratamento para prevenção de toxicidades graves induzidas por capecitabina Abstract: Colorectal cancer is the third most prevalent neoplasm worldwide ahead of gastric cancer, which is in the fifth position. Among the therapeutic options available for these neoplasms, capecitabine, which may be prescribed combined or not with other chemotherapic drugs, is noteworthy. It is an oral antineoplastic that, despite its high efficacy, has important toxicities associated with its use, and may be dose-limiting with a significant impact on patients' quality of life. The aim of this study was to evaluate the incidence of major toxicities in patients using capecitabine for the treatment of gastric and colorectal cancer and to correlate them with the presence of variants in the DPYD and MTHFR genes that are involved in important steps of the mechanism of action of this chemotherapeutic. This was an analytical, observational cohort study. Gastrointestinal, hematological, renal, dermatological, neurological, hepatic and fatigue toxicities were evaluated. The severity of these events was classified by the Common Toxicity Criteria for Adverse Events (version 4.0). The quality of life of the patient was also evaluated before the start of chemotherapy and after the third cycle of treatment through general and specific questionnaires for the type of cancer developed by the European Organization for Research and Treatment of Cancer and validated for Portuguese language. Adherence to treatment and knowledge of therapy were assessed using Morisky-Green and MedTake. Patients were genotyped for the following genetic variants by the real-time PCR technique: DPYD*5 (1627A> G), DPYD*9A (85T>C), MTHFR 677C>T and MTHFR 1298A>C. A total of 109 patients (58.61 ± 10.74 years, 51.38% male) were included, and the most frequent toxicities were: nausea, among those of gastrointestinal order; anemia, among those of hematological order; hand-foot syndrome among those of dermatologic order; paresthesia among those of neurological order and fatigue. Regarding general quality of life, there was a significant improvement in the "social function" and "pain" domains after the third treatment cycle. The majority of patients had high adherence to capecitabine and the level of knowledge regarding treatment improved significantly between patients over the first three treatment cycles. The DPYD*5 variant was correlated with an increase in non-clinically significant creatinine and a lower incidence of dysgeusia among patients, DPYD*9A with a decrease in non-clinically significant serum hemoglobin and a higher incidence of diarrhea and MTHFR 677C>T was associated with lymphopenia among study participants. Further studies need to be conducted in a larger group of patients to better assess the potential of these genetic variants in the pre-treatment screening for prevention of severe toxicities induced by capecitabine Mestrado Farmacologia Mestra em Farmacologia CNPQ CAPES 001

Le Lupus erythemateux aigue(LEA) chimio-induit est une affection rare, quelques cas ont ete rapporte dans la litterature incriminant la capecitabine, le paclitaxel et le docetaxel. Nous rapportons le cas d’une patiente âgee de 64 ans suivie pour carcinome canalaire invasif du sein droit, d’emble metastatique au niveau hepatique et ganglionnaire, sans antecedents de maladies auto-immunes ou d’allergie medicamenteuse. Apres une premiere ligne de chimiotherapie type AC60 (6 cures au total), elle a recu le docetaxel a la dose de 100 mg/m2, apres 5 cures elle a presente des lesions erythemateuses diffuses au niveaux des deux mains, des avants bras, des deux joues et en peribuccale, elle a ete mise sous corticotherapie avec protection solaire, on a pu poursuivre la meme chimiotherapie jusqu’a la huitieme cure. L’evolution a ete marque par la progression de sa maladie elle a ete mise sous capecitabine a la dose de 1250 mg/m2 deux fois par jours, apres six cures elle a presente des plaques erythemateux-squameuse et prurigineuse du visage, disposee en aille de papillon avec ulceration buccale et pulpite des doigts (Panel C) faisant evoque en premier un lupus erythemateux cutane aigue chimio-induit. Une biopsie a ete realisee qui etait en faveur d’une toxidermie lichenoide. Un bilan immunologique a ete demande pour eliminer un LEA chimio-induit, objectivant des anticorps anti DNA natif et des anticorps anti-histones negatifs, les anticorps anti-nucleaires sont positives a 320, ces derniers peuvent etre positives dans 50 a 70% des cas de cancer mammaire, ORL ou lymphome. Au vu de ces resultats le diagnostic de toxidermie est le plus probable.

Orientador: Gilberto de Nucci Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: O câncer é um grande desafio de saúde pública, gerando enormes custos e a sua prevalência tende a aumentar. A capecitabina é uma pró-droga de quimioterapia por via oral indicada no tratamento de câncer de mama e gastrintestinal. O objetivo deste estudo foi avaliar comparativamente a biodisponibilidade da capecitabina (um produto teste e o referência) a fim de determinar a bioequivalência para registro de um medicamento genérico, com menor custo para a população. Foi realizado um estudo de fase IV, monocêntrico, randomizado, aberto, cruzado, semi-replicado, em participantes sadios com 2 administrações em dose única de 150mg, em 3 períodos: formulação teste (1 ocasião) ou a formulação referência (em 2 ocasiões), após alimentação padronizada. Foi utilizada Cromatografia Líquida acoplada a Espectrometria de Massas (LC-MS-MS) para o método analítico, obtendo-se a razão geométrica de Cmax entre tratamentos de 104,0766 com I.C. 90% (88,1322; 122,9057), de ASC0-t 104,3403 e I.C. 90% (98,7468; 110,2506) e ASC0-inf 103,0665 e I.C. 90% (97,4852; 108,967). Os medicamentos se mostraram seguros e bem tolerados. Em conclusão, visto que o intervalo de confiança de 90% para a razão geométrica está dentro do intervalo definidos pelas autoridades regulatórias (80-125%), os produtos são bioequivalentes Abstract: Cancer is a major public health challenge, generating huge costs and its prevalence tends to increase. Capecitabine is an oral pro-drug chemotherapy indicated in the treatment of breast and gastrointestinal cancer. The objective of this study was to evaluate comparatively the bioavailability of capecitabine (a test product versus its reference), in order to determine the bioequivalence for registration of a generic drug, with lower cost for the population. A phase IV, monocentric, open-label, cross-over study in healthy subjects with 2 administrations in a single dose of 150mg, during 3 periods: test formulation (1 occasion) or the reference formulation (2 occasions) was performed under standardized fed conditions. Liquid chromatography coupled to mass spectrometry (LC-MS-MS) was used for the analytical method, obtaining a geometric ratio of Cmax among the treatments of 104.0766 with 90% CI (88.11322; 122.9057), AUC0-last 104.3403 and 90% CI (98.7468; 110.2506) and AUC0-inf 103.0665 and 90% CI (97.4852, 108.967). Medications were safe and well tolerated. In conclusion, since the 90% confidence interval for the geometric ratio is within the regulatory authorities accepted range (80-125%), the products are bioequivalent Mestrado Farmacologia Mestra em Farmacologia

BACKGROUND: The CAIRO3 and AIO 0207 trials demonstrated the efficacy of fluoropyrimidine plus bevacizumab (FP+Bev) maintenance treatment in metastatic colorectal cancer (mCRC) patients. In this individual patient data meta-analysis with updated follow-up, we aim to provide more precise estimates of treatment effects and to identify subgroups that benefit most from maintenance treatment or observation. METHODS: In 871 patients, randomised to FP+Bev maintenance treatment or observation, we investigated whether treatment effect was modified by sex, age, performance status, response to induction treatment, primary tumour location, number of metastatic sites, disease stage and primary tumour resection, serum LDH, platelet count, CEA, and RAS/BRAF mutation status. Primary end point was time to second progression after reintroduction of the induction regimen (PFS2). Secondary end points were first progression-free survival (PFS1) and overall survival (OS). RESULTS: At a median follow-up of 68.5 months (IQR 54.6-87.0 months), maintenance treatment was more effective compared with observation in PFS1 (HR 0.40(95% CI 0.34-0.47)) and PFS2 (HR 0.70(0.60-0.81)). No subgroups were identified that did not benefit from maintenance treatment in PFS1 and PFS2; no clinically relevant subgroup effects were observed. Regarding OS, pooled results were not significant (HR 0.91(0.78-1.05)), and the trials showed marked heterogeneity in overall treatment effect and subgroup effects. CONCLUSIONS: FP+Bev maintenance treatment is effective in all patients, regardless of the investigated subgroups. info:eu-repo/semantics/publishedVersion

Background: The introduction of oral antineoplastic agents in therapeutics has caused a change in the treatment strategy against cancer. The objective of this study was to analyze the adherence in patients to treatment with capecitabine, their adverse events, and the overall health status of patients, as well as the relationship of these factors with adherence. Method: An observational, prospective study at 7 months, in a cohort of patients on capecitabine treatment, including treatment initiations and continuations, regardless of diagnosis or indication. The data collected were: demographic variables (age, gender), diagnostic (breast cancer, colorectal cancer, gastric cancer, off-label), adherence (tablet count, Morisky test, Sackett test), safety (assessment of adverse events, clinical evaluation by the oncologist) and quality of life (performance status, SF-12 test). Data sources: electronic clinical records (IANUS®), dispensing program for outpatients (SILICON®) and interviews with patients. Results: There were 111 evaluable patients, with a mean age of 66.7 years (range 32-86), ECOG PS 1 in 76.6%. Adherence level: 78.4% (81.7% in the initiation subgroup vs. 72.5% in the continuation subgroup). Adverse events: skin toxicity (33.33%), asthenia (25.22%), gastrointestinal toxicity (24.32%) and neurological toxicity (24.32%), mostly G1. Health status, SF-12 test: subjective evaluation as “good” in 33.30% of cases. Conclusions: The low level of adherence in the continuation subgroup can be associated with the duration of treatment, toxicities, clinical evolution, and perception of their health status. It is necessary to conduct individualized monitoring in this group of patients in order to obtain a favorable clinical response. Resumen Introducción: La introducción en la terapéutica de antineoplásicos orales ha provocado un cambio en la estrategia de tratamiento frente al cáncer. El objetivo de este trabajo fue analizar la adherencia en pacientes en tratamiento con capecitabina, los acontecimientos adversos y el estado general de salud de los pacientes, así como la relación de estos factores con la adherencia. Método: Estudio observacional prospectivo, de siete meses de duración, en una cohorte de pacientes en tratamiento con capecitabina, incluyendo los inicios y las continuaciones de tratamiento, independientemente del diagnóstico o la indicación. Se registraron variables demográficas (edad, sexo), de diagnóstico (cáncer de mama, colon-recto, gástrico, off-label), de adherencia (recuento de comprimidos, test de Morisky, de Sackett), de seguridad (valoración de acontecimientos adversos, evaluación clínica del oncólogo) y calidad de vida (performance status, test SF-12). Fuentes de datos: historia clínica electrónica (IANUS®), programa de dispensación a pacientes externos (Silicon®) y entrevistas al paciente. Resultados: 111 pacientes evaluables, media de edad de 66,7 años (rango 32-86), ECOG PS 1 en el 76,6%. Nivel de adherencia: 78,4% (subgrupo inicio 81,7% vs. continuación 72,5%). Acontecimientos adversos: toxicidad cutánea (33,33%), astenia (25,22%), toxicidad gastrointestinal (24,32%) y neurológica (24,32%), en su mayoría G1. Estado de salud, test SF-12: valoración subjetiva “buena” en el 33,30%. Conclusiones: El bajo nivel de adherencia en el subgrupo de continuación puede relacionarse con la duración del tratamiento, las toxicidades, la evolución clínica y la percepción de su estado de salud. Es necesario un seguimiento individualizado en este grupo de pacientes para obtener una respuesta clínica favorable.

La capecitabina es una fluoropirimidina oral eficaz en el tratamiento del cáncer colorrectal. No obstante, la toxicidad asociada a este quimioterapéutico limita su uso como parte del manejo del paciente con este y otros tipos de neoplasias. En el medio costarricense se desconoce la incidencia de los efectos adversos de este agente citotóxico. Por tal motivo se diseño el presente estudio retrospectivo de análisis de registros médicos, cuyo objetivo principal fue establecer la incidencia acumulada de los eventos adversos secundarios al uso de este fármaco, cuando es empleado en pacientes con cáncer colorectal metastásico. Se incluyeron un total de 43 pacientes quienes cumplieron los criterios de inclusión. La dosis media inicial de capecitabina fue de 3000 mg/día en un 55,8% de los pacientes, la cual resultó menor a la dosis sugerida por el fabricante y recomendada en guías internacionales (2500mg/m2/día). Las reacciones adversas más frecuentes fueron: neuropatía (44.2%), diarrea (32.6%), vómitos y náuseas (30.2%), síndrome mano pie (23,3%), dolor abdominal (23,3%), pérdida de apetito (16,3%) y fatiga (9,3%). Conclusiones: A pesar del uso de la capecitabina a dosis menores de las recomendadas, este agente citotóxico presenta un perfil de eventos adversos de alta frecuencia en comparación con otras poblaciones.

Background: Capecitabine is known to rarely cause raised serum triglycerides (TG). In our centre, several patients receiving capecitabine developed raised TG levels corresponding to the ‘very high risk' category for potentially serious acute pancreatitis. Methods: A fasting blood lipid screening protocol was introduced into clinical practice for patients receiving capecitabine. Patients with TGs >5 mmol l−1 were treated and followed up. An 18-month prospective audit was performed to establish the incidence and severity of capecitabine-induced hypertriglyceridaemia (CIHT). Results: A total of 304 patients received capecitabine for colorectal cancer between January 2008 and June 2009. Of these, 212 patients (70%) were screened and 8 (3.7%) developed clinically significant hypertriglyceridaemia requiring lipid-lowering therapy. Two of the eight patients had diabetes and one had pre-existing dyslipidaemia. One suffered cerebral infarction during chemotherapy. There were no cases of acute pancreatitis. Follow-up showed that serum TGs safely and rapidly returned to normal with appropriate treatment without discontinuation of capecitabine. Conclusions: This is the first prospective study evaluating CIHT. These results suggest that it should be classed as a ‘common' undesired effect of capecitabine. Despite this, the incidence does not justify routine screening in all patients. Targeted screening in those with diabetes or pre-existing hyperlipidaemia is recommended, together with adoption of a clear management policy.

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.

Actas Dermosifiliogr. 2009;100:329-43 338 7. Chen GY, Chen YH, Hsu NM, Tsao CJ, Chen WC. Onychomadesis and onycholisis associated with capecitabine. Br J Dermatol. 2001;145:521-2. 8. Vazquez-Bayo C, Rodriguez-Bujaldon AL, Jimenez-Puya R, Galan-Gutierrez M, Moreno-Gimenez JC. Hiperpigmentacion secundaria a capecitabina. Actas Dermosifiliogr. 2007; 98:491-3. 9. Pui JC, Meehan S, Moskovits T. Capecitabine induced cutaneous hyperpigmentation: report of a case. J Drug Dermatol. 2002;1:202-5. 10. Tavares-Bello R. Capecitabine-induced hand-foot syndrome and cutaneous hyperpigmentation in an elderly vitiligo patient. J Eur Acad Dermatol Venereol. 2007;21:1434-5.

Actas Dermosifiliogr. 2009;100:329-43 338 7. Chen GY, Chen YH, Hsu NM, Tsao CJ, Chen WC. Onychomadesis and onycholisis associated with capecitabine. Br J Dermatol. 2001;145:521-2. 8. Vazquez-Bayo C, Rodriguez-Bujaldon AL, Jimenez-Puya R, G a l a n G u t i e r r e z M , M o r e n o G i m e n e z J C . Hiperpigmentacion secundaria a capecitabina. Actas Dermosifiliogr. 2007;98:491-3. 9. Pui JC, Meehan S, Moskovits T. Capecitabine induced cutaneous hyperpigmentation: report of a case. J Drug Dermatol. 2002;1:202-5.

Capecitabine, a prodrug of 5-fluorouracil (5-FU), is rarely associated with severe hypertriglyceridemia. We present a patient with severe capcitabine-induced hypertriglyceridemia, with the literature review.A 50-year-old woman with metastatic breast carcinoma was treated with oral capecitabine. She was also receiving bezafibrate due to hyperglycenemia. Pretreatment lipid profile revealed slight elevation of serum triglycerides and total cholesterol. A repeat lipid profile performed 5 weeks after the start of capecitabine treatment revealed a marked increase in the serum triglyceride and cholesterol levels. The dose of bezafibrate was increased, atorvastatin was added, and the next cycle of capecitabine was withheld. When the triglyceride and cholesterol levels had decreased, capecitabine was started with reduced dose. However, at the end of this cycle, the triglyceride and the cholesterol levels increased again.Monitoring of the lipid profile should be considered in cancer patients receiving capecitabine, particularly those with a known diagnosis of dyslipidemia.

Les antimetabolites sont des agents cytotoxiques qui n’ont plus de secrets pour les oncologues medicaux et pour les patients... ou presque. Quel patient n’a pas recu ou ne recevra pas du 5-FU ou du MTX dans l’evolution de sa maladie? Ecrire des nouvelles a propos des antimetabolites s’apparenterait-il alors a une gageure? C’est un defi que de vous parler encore de leur actualite en 2007..., car elle foisonne quoiqu’on en pense... Imaginez: 106 essais cliniques sont enregistres avec le pemetrexed (http://clinicaltrials-nccs.nlm.nih.gov consulte le 30 aout 2007)! ... Dans les trois classes d’antimetabolites, sans etre exhaustif, nous relaterons les derniers evenements, aussi bien pour les vieilles molecules (n’ayons pas peur des mots) que pour les molecules en developpement.

Im Rahmen von toxischen Arzneimittelreaktionen, insbesondere als Folge von Chemotherapien, zahlt die palmoplantare Erythrodysasthesie (PPE) mit einer Inzidenz von 6–64%, unter Capecitabine-Monotherapie von 10–24%, zu den haufigen unerwunschten Nebenwirkungen der Haut unter Chemotherapie. So sollte beim Auftreten von akralen Hauterscheinungen insbesondere unter Therapie mit Capecitabine (Xeloda®) differenzialdiagnostisch an eine PPE gedacht werden und eine Reduktion des Zytostatikums oder eine Anderung des Therapiemoduls veranlasst werden. In diesem Fallbericht wird erstmalig eine Patientin vorgestellt, die unter Capecitabine-Therapie das Krankheitsbild einseitiger akraler Nekrosen entwickelte, das als Abortivform einer PPE gewertet werden musste.

A 72-year-old patient with esophageal carcinoma developed a severe hand-foot syndrome during second-line therapy with the oral fluoropyrimidine capecitabine. We also summarize the current knowledge with regard to the hand-foot syndrome and distinguish it from palmoplantar erythrodysesthesia.

Jusqu'aux dernieres annees la question de la cardiotoxicite des antitumoraux concernait essentiellement les anthracyclines et le fluorouracile. A l'heure ou nombre de problemes semblaient en partie resolus notamment avec l'arrivee de cardioprotecteurs et de nouvelles formes galeniques, le developpement rapide des therapeutiques ciblees, trastuzumab en premier lieu mais egalement traitements antiangiogeniques, donne au probleme une dimension nouvelle.

The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice daily on days 1-14 plus i.v. bolus mitomycin C on day 1 at doses of 4, 6, 8 or 10 mg m(-2) (corresponding to dose levels I-IV). Cycles were repeated every 3 weeks. Two treatment cycles were considered for the evaluation of DLTs. Of the 53 patients enrolled, the majority had colorectal (n=27) or gastric (n=14) cancers. Patients had received a median of two lines of prior chemotherapy (34% with/=3 lines and 87% with prior 5-FU-based therapy). At the recommended dose level (IV, n=30), grade 3 adverse events during cycles 1 and 2 were: anaemia (10%); leukopenia (3%); thrombocytopenia (3%); stomatitis/mucositis (3%); hand-foot syndrome (3%). Two patients experienced DLTs (mucositis, n=1; neutropenic fever, n=1), but there were no grade 4 events. The median dose intensity for capecitabine and mitomycin C was 100% during cycles 1 and 2 and only four patients required postponement of therapy. Of the 43 patients evaluable for efficacy, seven achieved partial and minor remissions (16%; 95% CI, 5-28%), and 12 patients (28%) had stable disease. The favourable safety profile and promising activity of the capecitabine/mitomycin C combination, even in heavily pretreated patients, warrant further evaluation in patients with advanced colorectal and gastric cancers.

The goal in administering chemotherapeutics is to develop the ability to predict the outcome of therapy in terms of response and toxicity. Technology has been developed to allow tumor profiling with measurement of protein expression, gene expression levels of markers, and even genetic polymorphisms, which may predict response to particular chemotherapeutics. The chemotherapeutics for which particular markers have been shown to predict outcome include the fluoropyrimidines and platinums. The next step is to develop clinical trials that will assess prospectively the benefits of profiling a patient's particular tumor, which should translate into an improvement in response and toxicity.

Objectives: To evaluate the efficacy and safety of capecitabine in patients with advanced or recurrent gastric cancer, we conducted a pilot phase II study in Japan. Methods: Patients with advanced or recurrent gastric cancer were given oral capecitabine 828 mg/m2 twice daily for 3 weeks, followed by 1 week of no treatment. Two or more cycles were administered. From July 1996 to December 1997, 32 patients were enrolled in the study. The response to capecitabine was evaluated in 31 patients, excluding 1 found to be ineligible. Results: The overall response rate was 19.4% (6/31, 95% confidence interval: 7.5–37.5%). The median duration of response was 124.5 days, the median time to disease progression 85.0 days, and the median survival time 247.5 days. Drug-related adverse events of grade 3 or higher were infrequent: in 2 patients (6.3%) total bilirubin concentration increased, and 1 patient (3.1%) each had elevation of GOT, anemia, lymphopenia, increased creatinine, and hand-foot syndrome. No patient had gastrointestinal toxicity of grade 3 or higher. Conclusion: Capecitabine was suggested to be safe and effective in the treatment of advanced or recurrent gastric cancer. Further phase II studies of capecitabine on a large scale are warranted.

A series of 5-fluorocytosine derivatives, 5'-deoxy-N-alkyloxycarbonyl-5-fluorocytosine-5'-carboxylic acid 6, were synthesized and evaluated for their antitumor activity.

Introducción: Los tratamientos antineoplásicos orales presentan ventajas en cuanto a coste, comodidad y mejora potencial en la calidad de vida respecto al tratamiento endovenoso, pero es más difícil controlar la adherencia y monitorizar los efectos adversos. El objetivo de este estudio fue conocer la adherencia real en pacientes con antineoplásicos orales en nuestro centro, analizar la influencia de las características del paciente y del tratamiento, identificar motivos de no adherencia, oportunidades de mejora en la atención farmacéutica y evaluar la posible relación adherencia y respuesta al tratamiento. Método: estudio prospectivo observacional de cuatro meses de duración, en los pacientes con tratamiento antineoplásico oral dispensado desde la consulta de farmacia oncológica. Para la recogida de datos se utilizaron: orden médica, historia clínica y visita con entrevistas al paciente. Resultados: Se evaluaron un total de 141 pacientes. Un 72% se consideró totalmente adherente, mientras que en un 28% se detectó algún tipo de no adherencia. El tiempo desde el diagnóstico y la presencia de efectos adversos fueron las variables que afectaron a la adherencia. No se pudo demostrar relación entre adherencia y respuesta al tratamiento. Conclusiones: La adherencia al tratamiento antineoplásico oral en nuestro centro fue del 72%, identificando oportunidades de mejora en la atención farmacéutica dirigidas a prevenir los efectos adversos y a potenciar la adherencia de nuestros pacientes. Background: Oral chemotherapy agents offer advantages including cost, patient comfort and potential improvement in quality of life versus intravenous drugs. However ensuring adherence and monitoring adverse effects is more difficult. The aim of this study was to examine the real adherence in patients with oral chemotherapy agents in our hospital, to assess the influence of patient and treatment characteristics, to identify reasons for non adherence, to identify opportunities for improvement pharmaceutical care and to assess the potential relation between adherence and treatment outcomes. Method: observational, prospective study for a period of four month, in the patients who were dispensing oral chemotherapy agents in outpatient setting. The medical prescriptions, medical history and patient interviews were used to collect data. Results: 141 patients were assessing. 72% were considered as fully adherent, while 28% reported some kind of non adherence. Adherence was influenced by time from diagnosis and adverse effects. No relationship between adherence and treatment outcomes was found. Conclusions: Adherence to oral chemotherapy was 72%, identifing opportunities for improvement pharmaceutical care to prevent adverse effects and to improve our patient adherence.

Cette session de l’ASCO a confirme le role croissant des therapies ciblees dans le traitement du cancer du seinmetastatique.Mais, une fois n’est pas coutume, la presentation « vedette » concernait les patientes HER2-negatives, avec l’etude AVADO (Abstract LB 1011), testant la place du bevacizumab (B) en association au docetaxel (D) en premiere ligne metastatique. Le benefice de l’association bevacizumab et paclitaxel avait ete presente a l’ASCO 2005 (et publie en decembre dernier) conduisant a l’attribution d’une autorisation de mise sur marche (AMM) en 2007. Les resultats d’un schema incorporant ledocetaxel,plusclassiquedansnos protocoles, etaient tres attendus. Dans l’etude AVADO, 736 patientes ont ete randomisees pour recevoir, soit D 100 mg/m + placebo (P), soit D 100 + B 7,5 mg/kg, soit D 100 + B 15 mg/kg (schema j1-j21). Les patientes pouvaient recevoir au maximum neuf cycles de D, le bevacizumab etait poursuivi jusqu’a progression. Les caracteristiques des patientes etaient bien equilibrees dans les trois bras (environ 55 % de chimiotherapie adjuvante dont 15 % de taxanes, 41/49/49 % de patientes presentant trois sites metastatiques ou plus, 50/40/ 46 % de metastases hepatiques). L’objectif principal etait la mediane de survie sans progression (SSP), avec l’hypothese d’un gain de 2,6 mois (6 versus 8,6). Avec un suivi median de 10,2 mois, la SSP est significativement amelioree dans les deux bras incorporant le bevacizumab (hasard ratio [HR] respectif de 0,79 et 0,72), avec une mediane de 8 mois pour le bras placebo versus 8,7 et 8,8 mois pour les bras B 7,5 et B 15. On observe aussi une amelioration significative du taux de reponse objective (RO) ; lasurvieglobalen’estpas evaluable, puisque 80 % des patientes sont encore en vie dans chaque bras. Le benefice en SSP est retrouve pour tous les sous-groupes prevus dans l’analyse. L’administration de bevacizumab n’entraine pas de majoration significative de la toxicite (HTA, hemorragie, neutropenie...). Au total, meme si l’amplitude du benefice obtenu par l’adjonction de bevacizumab au docetaxel parait moindre qu’avec le paclitaxel, l’etudeAVADOconfirmecebenefice sur le taux de reponse et la survie sans progression. Ces deux etudes concordantes positionnent donc le bevacizumab comme une option possible en premiere lignemetastatique si le choixde la chimiotherapie s’est porte sur un taxane en monotherapie.

Background: Onycholysis, which is separation of the nail plate from the nail bed at its distal and lateral attachments, can cause pain and impair function and is a well-known side effect of traditional chemotherapeutic agents. Objectives: We present two cases of onycholysis associated with capecitabine in women with advanced breast cancer, who were initially referred for evaluation of onychomycosis and review the literature on capecitabine. Conclusion: Owing to the increased frequency of use of capecitabine for different cancers, physicians should be aware of this side effect.

For over four decades, 5-fluorouracil (5-FU) has been the mainstay of therapy for colorectal cancer and a major cytotoxic agent for treating gastrointestinal tumors and a variety of others, including breast and head and neck cancers. Xeloda® (capecitabine) is a new drug that is administered orally and has been rationally designed to generate 5-FU selectively within solid tumors. Theoretically, it has two major advantages, which should translate into an improved therapeutic index: firstly, enhanced drug concentration at the cancer site and therefore greater anti-tumor activity and secondly, reduced drug levels in non-tumor tissues, with a consequent reduction in systemic toxicity. After promising preclinical studies, phase I clinical trials of Xeloda have been performed with a variety of schedules, both with and without the oral biomodulator leucovorin. Anti-tumor activity has been observed with all regimens tested. In the setting of colorectal cancer, a randomized phase II study substantiated the phase I reports of activity and established the most promising regimen for phase III clinical trials. Patients in the phase II trial were randomly selected to receive either continuous Xeloda, intermittent Xeloda or intermittent Xeloda plus leucovorin. There were complete or partial responses in 21% of patients in the continuous arm, 24% in the intermittent arm, and 23% in the arm with intermittent Xeloda plus leucovorin. In addition, 51–63% of patients in each arm achieved stable disease. Therapy was well tolerated in all three arms. The intermittent regimen of Xeloda alone was associated with a longer time to disease progression and offered a one-week rest period to the patient. It was therefore selected for subsequent studies. Two randomized phase III trials of Xeloda versus the ’Mayo’ regimen in patients with advanced colorectal cancer have completed recruitment. They are designed to demonstrate at least equivalent efficacy, with important secondary endpoints of comparisons of toxicity, medical care utilization, and quality of life. No formal results are yet available from these studies. The same regimen of Xeloda is now being evaluated in a large scale adjuvant study, which is expected to recruit approximately 1,700 Dukes’ C colonic cancer patients (X-ACT study). The modest toxicity of Xeloda (particularly its low incidence of neutropenia) makes it a suitable candidate for novel combination therapies involving other agents that are active in colorectal cancer, including camptothecin and its analogues, oxaliplatin and radiotherapy. Further studies of Xeloda can be expected with other diseases known to be responsive to fluoropyrimidines, together with diseases traditionally thought to be resistant.