Study of Dosage-Dependent Effects of Cytostatic Drugs Using a Fibroblast Cell Culture of the Human Nasal Mucosa

Abstract Introduction Knowing a concentration at which cytostatic drugs are toxic for the nasal fibroblasts will enable the use cytostatic drugs in the clinical practice to prevent excessive cicatrization. Objective To determine the cytostatic concentrations of mitomycin С, doxorubicin, and 5-fluorouracil affecting nasal mucosa fibroblasts. Methods We obtained material during an endonasal dacryocystorhinostomy with the patient's informed consent. The cells were cultivated. Second- to fourth-passage cells were used in the experiments. The cells were stained for vimentin and cluster of differentiation 90 (CD90). An MTS test 3 (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium); cell viability test was performed. Results The cytostatic drugs have a toxic effect on cultivated fibroblasts of the nasal mucosa. This effect is dose-dependent. In terms of reducing the level of tissue fibrotisation in the nasal cavity, the most justified approach is to carry out an experimental study of the effect of mitomycin C, doxorubicin, and 5-fluorouracil at the concentrations of 0.25mg/ml, 0.25mg/ml, and 12.5mg/ml respectively. Conclusion The authors argue that it is inappropriate to use these cytostatic drugs to conduct studies with the goal of analyzing their antifibrotic effect on the nasal mucosa at concentrations that are either lower or higher than the aforementioned ones.

Efeitos da 5-iodotubercidina em linhagens de melanoma humano parentais e resistentes ao inibidor de BRAF / Effects of 5-iodotubercidin on human melanoma lines of parental and resistant to the BRAF inhibitor

O melanoma é responsável por menos de 5% dos cânceres de pele, porém, 95% das mortes ocorrem devido a ocorrência de metástases. O melanoma metastático é refratário às terapias convencionais e rapidamente adquire resistência às terapias como as oncogene-dirigidas, como o inibidor de BRAF, da via de MAPK. Estudos prévios de screening in silico do nosso grupo, onde se utilizou as bases de dados TCGA e GEO, identificaram o gene adenosina quinase (ADK) como sendo diferencialmente expresso entre o melanoma invasivo e os nevus. A 5-iodotubercidina (5-ITu) é um potente inibidor farmacológico da ADK que dentre os diversos efeitos relatados na literatura destaca-se pelo potencial genotóxico. Os danos no DNA são os principais ativadores de checkpoint do ciclo celular, que levam a parada do ciclo celular transitória ou permanente, além de induzir morte celular, levando a hipótese de que ADK possa ser potencial agente anti-melanoma. Este trabalho objetivou avaliar a expressão do gene ADK em melanomas humanos e quimiorresistentes ao inibidor de BRAF (iBRAF), avaliou os impactos de 5-ITu sobre a proliferação, progressão do ciclo celular e morte celular e por fim avaliamos sua capacidade de aumentar a sensibilidade das células. Foi realizado PCR em tempo real para avaliar os níveis de expressão de mRNA de ADK em linhagens de melanoma e na cultura primária de melanócitos; a fim de avaliar a citotoxicidade de 5-ITu foram realizados os ensaios de exclusão por azul de tripan e de apoptose - Anexina V e PI e em modelo de esferoide, usando live/dead; também foi avaliada a influência de 5-ITu sobre a capacidade clonogênica e seus efeitos sobre a proliferação celular, a partir dos ensaios de ciclo celular e avaliação de marcadores de proliferação por imunofluorescência; as linhagens foram submetidas a diferentes regimes de tratamento com 5-ITu e o iBRAF, a fim de avaliar a curva de crescimento e a sensibilidade ao iBRAF por MTT níveis de expressão de mRNA de ADK maiores nas linhagens tumorais em relação aos melanócitos. 5-ITu mostrou-se capaz de inibir a proliferação (IC50) das linhagens de melanoma em concentrações de 1,9 a 3,5 µM. 5-ITu não foi capaz de induzir inviabilidade celular, apesar de reduzir a quantidade de células viáveis em todas as condições de tratamento, também não foi capaz de induzir aumento significativo de células apoptóticas, nem mesmo necróticas. No entanto, o tratamento com 5-ITu reduziu a capacidade clonogênica de linhagens de melanoma e promoveu parada de ciclo celular nas fases G1 e G2/M, levou ao aumento da população subG1. O tratamento com 5-ITu promoveu a redução da expressão de marcadores de proliferação, como ki67, e a combinação de tratamentos 5-ITu e iBraf foi capaz de aumentar o tempo de dobramento das linhagens de melanoma, embora tenha se mostrado incapaz de sensibilizar as células de melanoma ao tratamento com iBRAF. Desse modo, pode-se concluir que 5-ITu induz o efeito citostático e se mostra um potente agente antiproliferativo para melanoma parental e resistente

Melanoma accounts for less than 5% of skin cancers, but 95% of deaths occur due to metastases. Metastatic melanoma is refractory to conventional therapies and rapidly acquires resistance to therapies such as oncogene-directed, such as the BRAF inhibitor, of the MAPK pathway. Previous studies of screening in silico of our group, using the databases TCGA and GEO, identified the adenosine kinase gene (ADK) as differentially expressed between invasive melanoma and nevus. 5-iodotubercidin (5-ITu) is a potent pharmacological inhibitor of ADK that among the several effects reported in the literature stands out for the genotoxic potential. DNA damage is the main activator of the cell cycle checkpoint, which leads to transient or permanent cell cycle arrest, in addition to inducing cell death, leading to the hypothesis that ADK may be a potential anti-melanoma agent. This work aimed to evaluate the expression of the ADK gene in human melanomas and chemoresistants to the BRAF inhibitor (iBRAF), evaluated the impacts of 5-ITu on proliferation, cell cycle progression and cell death and finally we evaluated its ability to increase the sensitivity of cells. Real-time PCR was performed to assess the levels of ADK mRNA expression in melanoma lines and primary melanocyte culture; in order to evaluate the cytotoxicity of 5-ITu, the trypan blue and apoptosis - Annexin V and PI exclusion and blue spheroid models were performed using live / dead; the influence of 5-ITu on the clonogenic capacity and its effects on cell proliferation, from the cell cycle assays and the evaluation of proliferation markers by immunofluorescence; the cell lines were submitted to different treatment regimens with 5-ITu and iBRAF in order to evaluate the growth curve and the sensitivity to iBRAF by MTT levels of mRNA expression of ADK higher in the tumor lines in relation to the melanocytes. 5-ITu was able to inhibit the proliferation (IC 50) of melanoma lines at concentrations of 1.9 to 3.5 181;M. 5-ITu was not able to induce cell non-viability, although it reduced the amount of viable cells in all treatment conditions, nor was it able to induce a significant increase in apoptotic or even necrotic cells. However, treatment with 5-ITu reduced the clonogenic capacity of melanoma cells and promoted cell cycle arrest in the G1 and G2 / M phases, leading to an increase in the subG1 population. Treatment with 5-ITu promotes the reduction of expression of proliferation markers, such as ki67, and the combination of 5-ITu and iBRAF treatments was able to increase the doubling time of melanoma cells, although it has been shown to be unable to sensitize melanoma cells to treatment with iBRAF. Thus, it can be concluded that 5-ITu induces the cytostatic effect and shows a potent antiproliferative agent for parental and resistant melanoma

Extravasación de citostáticos por vía periférica. tratamiento quirúrgico: ¿cuándo y cómo? / Extravasation of peripheral cytostatic. surgical treatment: when and how?

Se analiza el tratamiento quirúrgico en las extravasaciones de citostáticos por vía periférica. Se discute cuándo y cómo realizarlo. Se lo ubica dentro del contexto de los otros dos tratamientos: el de urgencia y el clínico. Se señala que el tipo de citostático utilizado y el estado clínico de paciente influyen en esta decisión.

Surgical treatment in peripheral cytostatic extravasations is analysed. It discusses when and how to perform it. It is placed within the context of the other two treatments: the emergency and the clinical. It is pointed out that the type of cytostatic used and the clinical status of the patient influence this decision.

Anemia en pacientes con cáncer expuestos a quimioterapia / Anemia in patients with cancer exposed to chemotherapy

Se efectuó un estudio descriptivo y transversal de 146 pacientes con cáncer atendidos en el Servicio de Quimioterapia del Hospital Oncológico Docente Provincial "Conrado Benítez García" de Santiago de Cuba, de enero a junio del 2015, con el objetivo de describir la variación de las anemias antes y después de aplicada la quimioterapia, según las variables edad, sexo, localización tumoral, grado de anemia y agente citostático empleado. En la serie predominaron las pacientes en las edades de 41-60 años (46,5 %) y el cáncer de mama (62,3 %), y las medias de hemoglobina antes y después del tratamiento fueron de 113,08 y 104,77 g/L, respectivamente. Antes de recibir los citostáticos 110 pacientes (75,6 %) padecían anemia, principalmente en la forma leve (60,0 %). No se demostró asociación entre los grados de las anemias y el tratamiento con platinos; no obstante, sí existió un mayor número de pacientes con anemia después de la quimioterapia, sobre todo en el grado leve.

A descriptive and cross-sectional study of 146 patients with cancer assisted in the Chemotherapy Service of "Conrado Benítez García" Teaching Oncological Provincial Hospital in Santiago de Cuba, was carried out from January to June, 2015, aimed at describing the variation of anemias before and after having applied the chemotherapy, according to variables such as age, sex, tumoral localization, degree of anemia and cytostatic agent. In the series the patients aged 41-60 years (46.5%) and the breast cancer (62.3%) prevailed, and the mean hemoglobin before and after the treatment were 113.08 and 104.77 g/L, respectively. Before receiving the cytostatic 110 patients (75.6%) suffered from anemia, mainly in the light form (60.0%). The association between the degrees of anemias and the treatment with platinums was not demonstrated; nevertheless, there was a higher number of patients with anemia after the chemotherapy, mainly in the light degree.

Neutropenia inducida por quimioterapia en pacientes con cáncer de mama / Neutropenia induced by chemotherapy in patients with breast cancer

Se realizó un estudio descriptivo, transversal y prospectivo de 201 pacientes con cáncer de mama atendidos en el Servicio de Quimioterapia del Hospital Oncológico Docente Provincial "Conrado Benítez García" de Santiago de Cuba durante un año (de junio del 2013 a igual mes del 2014), a fin de caracterizarles y determinar la presencia de neutropenia como reacción adversa al tratamiento. La información fue analizada estadísticamente mediante el cálculo porcentual y la prueba de la Χ², con lo cual se obtuvo que 82 pacientes padecieran neutropenia (40,7 %), en quienes predominó el grupo etario de 41-60 años (50,0 %), el estadio clínico II del tumor maligno (65,8 %) y un único episodio de neutropenia (90,2 %). En cuanto a las pacientes diagnosticadas con neutropenia, se registraron 91 episodios, con mayor frecuencia de los grados moderado (52,7 %) y leve (39,5 %), y una reacción favorable al factor estimulante de colonias de granulocitos humano en 81,8 % de ellas. Por último, se demostró la existencia de neutropenia como efecto adverso a los citostáticos en casi 50 % de las pacientes, así como el resultado beneficioso del factor estimulante en estas; sin embargo, no se halló asociación entre las diferentes combinaciones de citostáticos y los episodios y grados de neutropenia.

A descriptive, cross-sectional and prospective study of 201 patients with breast cancer assisted in the Chemotherapy Service of "Conrado Benítez García" Teaching Provincial Oncological Hospital in Santiago de Cuba was carried out during a year (from June, 2013 to the same month of 2014), in order to characterize them and to determine neutropenia as adverse reaction to the treatment. The information was analyzed statistically by means of the percentage calculation and the test Chi squared test, with which it was obtained that 82 patients suffered neutropenia (40.7%) in whom the age group 41- 60 years prevailed (50.0%), the clinical stage II of the malignant tumor (65.8%) and just one neutropenia episode (90.2%). As for the patients diagnosed with neutropenia, 91 episodes were registered, with higher frequency of the moderated degrees (52.7%) and mild (39.5%), and a favorable reaction to the stimulating factor of human granulocytes colonies 81.8% of them. Lastly, the neutropenia existence as adverse effect to the cytostatic drugs in almost 50% of the patients was demonstrated, as well as the beneficial result of the stimulating factor in them; however, there was no association between the different combinations of cytostatic drugs and the episodes and neutropenia degrees.

Identificación, análisis y evaluación del riesgo de exposición ocupacional en servicios de preparación de citostáticos de la Red Nacional de Prestadores / Identification, analysis and risk assessment of occupational exposure in cytostatic preparation services of the Providers National Network

Se identifica, analiza y evalúa el riesgo de exposición ocupacional a citostáticos, en una muestra de instalaciones destinadas a preparación de mezclas destinadas a tratamiento terapéutico oncológico, pertenecientes a la Red Nacional de Prestadores autorizados; en relación con el tipo y nivel de infraestructura de control y frecuencia de exposición asociada. Los resultados de la evaluación revelan una gran variedad de situaciones en las que, pese a la existencia de una regulación que define el tipo y caracteristicas de la contención mínima necesaria, se observan insuficiencias en el nivel de control observado y consiguiente riesgo al que se expone el personal. Del total de instalaciones incluidas en el estudio, sólo el 7% presenta un nivel de control aceptable y cercano al óptimo esperado, el 43% presenta un nivel de control regular y mejorable a través de correcciones menores. En tanto el 50% restante, revela un significativo nivel de insuficiencia; destacando que el 36% de las instalaciones evidencia condiciones extremas de exposición laboral.

The risk of occupational exposure to cytostatic was identified, analyzed and evaluated, in a sample of facilities used for preparation of mixtures for oncological therapeutic treatment, belonging to the National Network of Authorized Providers; regarding the type and level of infrastructure of control and frequency of associated exposure. The results of the evaluation reveal a great variety of situations where, despite the existence of a regulation that defines the type and characteristics of the minimum containment required, gaps are observed in the observed level of control and consequent risk which personnel is exposed to. From the total number of facilities included in the study, only 7% have a level of control acceptable and close to the optimal that is expected, 43% present a control level that is regular and improvable through minor corrections. Meanwhile, the remaining 50% show a significant level of insufficiency; it is underlined that 36% of facilities evidence extreme occupational exposure conditions.

Evaluación de la exposición ocupacional a Ciclofosfamida en nueve hospitales del Perú / Evaluation of occupational exposure to Cyclophosphamide in nine hospitals of Peru

Objetivos. Evaluar la exposición ocupacional a ciclofosfamida en nueve hospitales del Perú. Materiales y métodos. Estudio observacional de tipo transversal realizado durante el año 2010 en el cual se colectó muestras de orina de 24 h de 96 trabajadores de las unidades de mezclas oncológicas y servicios de oncología de nueve hospitales del Perú, la cuantificación de ciclofosfamida se realizó por la metodología de GC-MS ( Gas Cromathography-Mass Spectroscopy). Se realizó, además, muestreo de superficies de trabajo utilizando paños húmedos para la determinación de ciclofosfamida. Resultados. Se detectó la presencia de ciclofosfamida en orina en 67 trabajadores (concentración promedio de excreción: 74,2 ng/24 h), lo cual representa el 70% del total de la población evaluada. Basado en la excreción se puede clasificar la exposición total entre los hospitales, en términos de exposición alta (>18,9 ng/24 h), moderada (1,725 - 18,9 ng/24 h) y baja (<1,725 ng/24 h), con una frecuencia porcentual de 31,3; 26,0 y 42,7% respectivamente. Además, como parte de la evaluación ambiental, se encontró concentraciones de ciclofosfamida de 14,72, 14,98 y 5,12 ng/cm².Conclusiones. Se evidencia una contaminación por ciclofosfamida en las áreas donde se realizan los preparados oncológicos y la presencia de ciclofosfamida en muestras de orina de trabajadores expuestos a citostáticos.

Objetives. Evaluate occupational exposure to cyclophosphamide in nine hospitals of Peru. Materials and methods. Cross-cutting observational study conducted in 2010, for which 24-hour urine samples were obtained from 96 employees of the oncologic mixture units and oncology services of nine hospitals in Peru, the quantification of cyclophosphamide was done through the GC-MS methodology ( Gas Cromathography-Mass Spectroscopy). Additionally, working surfaces were tested by obtaining samples with wet wipes for identification of cyclophosphamide. Results. Cyclophosphamide was detected in urine samples in 67 employees (average concentration of excretion: 74.2 ng/24 h), accounting for 70% of the total population to be assessed. Based on the excretion, total exposure among hospitals can be classified as high level (>18.9 ng/24 h), moderate level (1,725 - 18.9 ng/24 h) and low level (<1,725 ng/24 h), with a percent incidence of 31.3; 26.0 and 42.7% respectively. Additionally, as part of the environmental evaluation, concentrations of cyclosphamide were found in 14.72, 14.98 and 5,12 ng/cm2. Conclusions. Contamination through cyclophosphamide in areas where oncological preparations are done and the presence of cyclophosphamide in urine samples of workers exposed to cytostatics substance were observed.

Individualización de dosis en el paciente oncológico con insuficiencia hepática / Customization of doses in oncological patients with impaired hepatic function

Objetivo: determinar qué citostáticos requieren ajuste de dosis en pacientes con insuficiencia hepática. Métodos: se realizó una búsqueda en PubMed de toda la bibliografía publicada hasta julio de 2011 sobre dosificación de citostáticos en pacientes con función hepática alterada. Se procedió a su valoración según la clasificación de la Scottish Intercollegiate Guidelines Network. Se sintetizó un índice de fuerza de la recomendación farmacoterapéutica, para lo que se asoció el grado de recomendación de la evidencia encontrada y el número de pacientes incluidos en los estudios encontrados. Se clasificó la recomendación para cada fármaco como de fuerza alta, media o baja. Resultados: se encontraron un total de 46 publicaciones con información sobre dosificación en pacientes con insuficiencia hepática para un total de 17 citostáticos. El 67 por ciento (n= 31) de las publicaciones fueron estudios de cohortes con un nivel de evidencia 2+. No pudieron establecerse recomendaciones de fuerza alta, pero sí de fuerza moderada (76 por ciento; 13 fármacos) y baja (24 por ciento; 4 fármacos). Conclusiones: aunque el nivel de la evidencia disponible fue bajo, podrían establecerse recomendaciones sobre la dosificación de citostáticos en pacientes con insuficiencia hepática para mejorar la seguridad en el uso de estos fármacos en el referido grupo de enfermos(AU)

Objective: to determine the cytostatic drugs requiring dose adjustment in patients with impaired hepatic function. Methods: aliterature review of all the papers about dosage of cytostatic drug in patients with impaired hepatic function published till July 2011 in Pubmed search was made. They were assessed as rated by the Scottish Intercollegiate Guidelines Network. An index of pharmacotherapy recommendation strength was developed, for which the grade of recommendation of the evidence found and the number of patients included in the studies were then correlated, ranking the strength of recommendation for each drug as high, medium or low. Results: atotal of 46 publications with information about dosing in liver failure were found for 17 cytostatic drugs. Sixty seven percent (n= 31) of the publications were cohort studies with a level of evidence 2+. High strength recommendations could not been established, but moderate strength (76 percent; 13 drugs) and low strength (24 percent; 4 drugs) recommendations were finally established. Conclusions: although level of evidence was low, dosage recommendations of cytostatic drugs to be used in liver failure patients were established to improve safety in the use of these drugs in the stated group of patients(AU)

Citotoxicidad in vitro de extractos laticiferos de Calotropis procera (Aiton) W.T. Aiton y Pedilanthus tithymaloides (L.) Poit / In vitro cytotoxicity of laticifers extracts from Calotropis procera (Aiton) WT and Pedilanthus tithymaloides (L) Poit

In order to assess the anticancer action of extracts obtained by latex from Calotropis procera and Pedilanthus tithymaloides, samples were collected from adult plants. Soluble proteins were extracted with 16 uL of 50 mM sodium acetate pH 5/ug integral latex and centrifugation at 16,000 x g for 15 min, the supernatant was named "latex crude extract" (LCE). The "latex methanolic extract" (LME) was obtained on dried latex. Both extracts were tested in vitro by cytotoxic and cytostatic activity in Jurkat cell cultures. Cellular viability, proliferation, necrosis and apoptosis were evaluated. LCE and LME of C. procera were found with cytotoxic and cytostatic activity after 24 incubation hours (p < 0,05) with doses from 1ug/mL. The LCE and LME of P. tithymaloides presented cytotoxic effect (p < 0,05) from 50 ug/mL and from 1ug/mL, respectively.

Con el objetivo de evaluar el potencial anticanceroso de extractos de látex de Calotropis procera y Pedilanthus tithymaloides se colectaron muestras de plantas adultas. Las proteínas solubles fueron extraídas con 16 uL de acetato de sodio 50 mM pH 5/ug de látex integral y centrifugación a 16.000 x g durante 15 min, denominándose al sobrenadante “extracto crudo de látex” (ECL). El “extracto metanólico de látex” (EML) se obtuvo sobre látex deshidratado. Ambos extractos fueron probados en su actividad citotóxica y citostática in vitro sobre cultivos de células Jurkat. Se realizaron estudios de viabilidad, proliferación, necrosis y apoptosis celular. El ECL y el EML de C. procera presentaron actividad citotóxica y citostática después de 24 y 48 horas de incubación (p < 0,05) con dosis desde 1 ug/mL. Los ECL y EML de P. tithymaloides presentaron efectos citotóxicos (p < 0,05) a partir de 50 ug/mL y desde 1 ug/mL respectivamente.

The effects of 5-aza-2'-deoxycytidine on proliferation and cell cycle of MCF-7/ADR cells and KBV/200 cells and their mechanism / 肿瘤

Objective: To investigate the effect of 5-Aza-dC (5-aza-2'-deoxycytidine) on cell cycle of multidrug resistant cells and its mechanism. Methods: Inhibitory effects of 5-Aza-dC on proliferation of breast cancer MCF-7/ADR cells and oral epidermoid carcinoma KBV/200 cells were detected by MTT method. The changes of cell cycle distribution were examined by flow cytometry when the cells were treated with 5-Aza-dC at different concentrations for 72 h or treated with the same concentration of 5-Aza-dC (10 μmol/L) for different time. The expression levels of cyclin A, cyclin E and p21waf1/cip1 mRNAs and proteins were detected by real-time fluorogenic quantitative-PCR and Western blotting, respectively. Results: The proliferation of MCF-7/ADR and KBV/200 cells was suppressed significantly after 5-AzadC treatment. The cell cycle was arrested at G2/M phase in dose- and time-dependent manners. The expression levels of cyclin A, cyclin E and p21waf1/cip1 mRNAs and proteins were elevated. Conclusion: The cell cycle of MCF-7/ADR and KBV/200 cells can be arrested at G2/M phase which consequently results in the inhibition of proliferation of multidrug resistant cells induced by 5-Aza-dC. The molecular mechanisms may be related with up-regulation of expressions of cyclin A, cyclin E and p21waf1/cip1 mRNAs and proteins. Copyright © 2012 by TUMOR.

Detección de errores potenciales de prescripción de carboplatino mediante validación farmacéutica / Detection of potential prescription errors of carboplatin by pharmaceutical validation

Las fallas en alguno de los procesos de la farmacoterapéutica podrían ser un riesgo potencial para que se cometan errores que puedan provocar daños en el paciente. Por este motivo todo servicio que aplique terapéutica citostática a sus pacientes debe establecer un procedimiento de validación de sus procesos, comenzando por la prescripción. En el presente trabajo se realizó un análisis del comportamiento de este proceso en las prescripciones que incluyeron el carboplatino, citostático cuyos efectos adversos son en general, frecuentes, moderadamente importantes y cuyas dosis deben ser ajustadas individualmente teniendo en cuenta el aclaramiento estimado y el área bajo la curva. Se realizó un estudio descriptivo retrospectivo con el objetivo de identificar las deficiencias en el transcurso de la validación farmacéutica de este fármaco, incluido en los esquemas de tratamientos de quimioterapia en pacientes con cáncer de pulmón. Fueron seleccionadas 45 órdenes médicas de pacientes comprendidos en grupos de edades mayores de 51 años, con comportamiento similar en uno y otro sexo y en los cuales predominó el cáncer de pulmón de células no pequeñas. Prevalecieron los errores sin daño de tipo B (64), seguidos de los errores sin daño tipo C (21). Los errores potenciales de tipo A se presentaron con una frecuencia de 26 oportunidades, en 8 de ellas no se indicó el área bajo la curva y en 18 no hubo cambio de dosis en los diferentes ciclos. Se concluye que el proceso de validación farmacéutica es vital para prevenir que los errores en la prescripción lleguen al paciente

All failures in some of the pharmacotherapy processes could be a potential risk to make mistakes that could to provoke damages in the patient. Thus, all service applying a cytostatic therapy to its patients must to establish a validation procedure of processes, beginning by prescription. In present paper an analysis of behavior of this process in the prescriptions was made including the carboplatin, cytostatic agent whose adverse effects are in general frequent, moderately significant and whose doses must to be adjusted taking into account the estimated clearance and the area under curve. The aim of present paper was to conduct a retrospective and descriptive study to identify the deficiencies during the pharmaceutical validation of this drug, included in the schemes of chemotherapy treatment in patients presenting with lung cancer. A total of 45 medical prescriptions were selected from patients aged over 51 with a similar behavior in both sexes where the non-small cells lung cancer was predominant, prevailing the error without type B damage (64) followed by error without type C damage (21). The potential type A errors were present in 26 opportunities; in eight of them the area under the curve was not signaled and in 18 there was not a dose change during the different cycles. We conclude that the pharmaceutical validation process is essential to avoid that the errors in prescription to reach patient

Aparición de episodios de neutropenia febril tras la quimioterapia citostática en el paciente oncológico / Appearance of febrile neutropenia episodes after cytostatic therapy on Oncology patients

El tratamiento con drogas citotóxicas en el paciente oncológico, tiene como toxicidad limitante de dosis más común la neutropenia y sus complicaciones infecciosas. Su aparición provoca retrasos y reducción de dosis en los ciclos posteriores de quimioterapia, así como deterioro en la calidad de vida de los pacientes. El colectivo de Medicina Oncológica, que incluye el Servicio de Farmacia, decidió realizar un estudio, con el objetivo de analizar la aparición de neutropenia febril tras la administración de la terapia citotóxica y la presencia de otros factores que pueden incrementar el riesgo de estas reacciones. Se estudiaron los 42 pacientes que ingresaron con neutropenia febril tras el tratamiento citotóxico en el periodo comprendido entre febrero y agosto del 2007. Se recogieron variables biomédicas del grupo de pacientes incluidos y se analizó el tratamiento citostático empleado previamente. El grupo de edad que prevaleció fue el de los pacientes mayores de 50 años, con un predomino del sexo masculino y los estadios avanzados con afecciones asociadas. Las localizaciones tumorales más frecuentes radicaron en mama, pulmón y linfoma no Hodgkin. El citostático más señalado en casos de neutropenia febril resultó la adriamicina con un 71,4 %, seguido de la ciclofosfamida con 52,4 %. Los factores que más se asociaron con la aparición de neutropenia febril fueron: quimioterapia con antraciclinas, la edad mayor de 50 años, estadios avanzados y presencia de enfermedades asociadas.

Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and the presence of other factors that may to increase the risk to these reactions. A total of 42 patients were studied admitted with febrile neutropenia after above therapy from February to August, 2007. Biomedical variables from included patient group were achieved and the previously applied cytostatic therapy. The prevalent age-group was those patients aged over 50 and predominance of male sex and advanced stages with associated affections. The more frequent tumor locations were in breast, lung, and non-Hodgkin lymphoma. The cytostatic agent more used in cases of febrile neutropenia was Adriamycin (71.4 %) followed by Cyclophosphamide (52.4 %). The factors more associated with febrile neutropenia appearance were: Anthracycline chemotherapy, age over 50, advanced stages, and presence of associated diseases.

Citostáticos: medicamentos riesgosos / Cysatostatic drugs: risky drugs

Se hizo una revisión bibliográfica concerniente a los posibles riesgos ocupacionales que entraña la manipulación de medicamentos antineoplásicos. Se ha demostrado, en estudios clínicos, que estos medicamentos poseen efectos carcinogénicos, mutagénicos y teratogénicos. Por lo tanto, los trabajadores expuestos ocupacionalmente a estos compuestos pueden enfrentar graves peligros para su salud si no siguen una serie de normativas establecidas que regulan el adecuado manejo de estos medicamentos.

A bibliographic review concerning the possible occupational risks of the antineoplastic drugs handling was made. It has been proven in clinical studies that these drugs have carcinogenic, mutagenic and teratogenic effects. Therefore, those workers occupationally exposed to these compounds may face severe dangers for their health if they do not follow a series of measures established to regulate the adequate handling of these drugs.