Evaluación de la interacción de capecitabina con inhibidores de la bomba de protones en pacientes con cáncer de colon metastásico / Evaluation of the interaction of capecitabin with proton pump inhibitors in patients with metastatic colon cáncer

Objetivo: Evaluar el impacto clínico que la interacción de capecitabina con inhibidores de la bomba de protones (IBP) puede tener sobre la efectividad del tratamiento de mantenimiento en pacientes con cáncer de colon metastásico (CCm). Material y métodos: Estudio retrospectivo, observacional descriptivo que incluyó a todos los pacientes con CCm tratados con capecitabina sola o en combinación entre enero 2013-diciembre 2016. Los pacientes fueron divididos en dos grupos según si fueron o no tratados con IBP concomitantemente con capecitabina. Se evaluaron variables demográficas, farmacológicas y clínicas, siendo la supervivencia libre de progresión (SLP) la variable elegida para evaluar el impacto clínico de la interacción. Resultados: Se incluyeron 150 pacientes. De ellos, el 57,33% varones, media de edad 70,10±12,06 años; el 55,33% tuvieron un ECOG 1 y el 58,67% utilizaron IBP. Un 39,33% fueron tratados con capecitabina en monoterapia, 31,33% CapeOx, y 20% capecitabina+bevacizumab y 9,33% CapeOx+bevacizumab. El 53,33% tuvo un tratamiento basado en capecitabina en primera línea, la frecuencia de variaciones de tratamiento fue de 42,0% reducción de dosis, 38,0% retraso, y 12% interrupción tratamiento. El 78,0% presentó alguna toxicidad, destacando 34,67% diarrea y 30,0% (síndrome mano-pie). La SLP media fue de 6,69 vs 6,0 meses (HR=0,97; IC95% 0,68-1,39; p=0,87) en favor de los pacientes que no utilizaron IBP, aunque la relación fue no significativa. Conclusiones: En la población estudiada, los pacientes con CCm que recibieron tratamiento de mantenimiento basado en capecitabina y que utilizaron IBP simultáneamente, presentaron una tendencia no significativa a la disminución de la SLP. (AU)

Objective: To evaluate the clinical impact that the interaction of capecitabine with proton pump inhibitors (PPIs) may have on the effectiveness of maintenance treatment in patients with metastatic colon cancer (mCC). Material and methods: Retrospective, observational, descriptive study that included all patients with CCm treated with capecitabine alone or in combination between January 2013-December 2016. The patients were divided into two groups according to whether or not they were treated with PPIs concomitantly with capecitabine. Demographic, pharmacological and clinical variables were evaluated, with progression free survival (PFS) being the variable chosen to evaluate the clinical impact of interaction. Results:150 patients were included. Of them, 57.33% were men, mean age 70.10±12.06 years; 55.33% had an ECOG 1 and 58.67% used it in PPIs. 39.33% were treated with capecitabine in monotherapy, 31.33% CapeOx, and 20% capecitabine+bevacizumab and 9.33% CapeOx+bevacizumab. 53.33% had a first-line capecitabine-based treatment, the frequency of treatment variations was 42.0% dose reduction, 38.0% delay, and 12% treatment interruption. 78.0% presented any toxicity, (highlighting 34.67% diarrhea and 30.0% hand-foot syndrome). The mean PFS was 6.69 vs 6.0 months (HR=0.97; 95% CI 0.68-1.39; p=0.87) in favor of patients who did not use IBP, although the relationship was not significant. Conclusions: In the population studied, patients with mCC who received maintenance treatment based on capecitabine and who used PPIs simultaneously, showed a non-significant trend towards a decrease in PFS. (AU)

[Incidence of intravenous colistin nephrotoxicity in hospitalized patients]. / Incidencia de nefrotoxicidad inducida por colistina intravenosa en pacientes hospitalizados.

OBJECTIVE: The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. The aim of the study is to determine the incidence of colistin nephrotoxicity nowadays. METHODS: Retrospective-observational-unicentric study was collected hospitalized patients in intravenous colistin treatment during the years 2018-2019. Nephrotoxicity was defined according to the RIFLE scale. The variables to determine it were serum creatinine (sCr) and glomerular filtration (GF). The variables analyzed were age, sex, treatment duration, loading and cumulative dose, empirical/targeted treatment, chronic kidney disease, concomitant use of intravenous contrast and nephrotoxic drugs. RESULTS: A total of 90 patients (60% men) were included, with an average age of 58.2±18.1 years. The mean duration of treatment was 9±8.3 days, with an average cumulative dose of 69.8±71MU. There were no differences between sCr and GF at the beginning and end of treatment. The incidence of nephrotoxicity was 1.73 cases/100 days of treatment (prevalence of 15.56%). CONCLUSIONS: Colistin nephrotoxicity has an important incidence, without developing severe illness.

Efectividad y seguridad de daratumumab y carfilzomib en el tratamiento del mieloma múltiple refractario / Effectiveness and safety of daratumumab and carfilzomib in the treatment of multiple refractory mieloma

Objetivos: El objetivo del estudio es evaluar la efectividad y seguridad de daratumumab y carfilzomib en práctica clínica, y comparar estos resultados con la literatura disponible y ficha técnica.Material y métodos: Estudio retrospectivo y observacional donde se recogieron pacientes en tratamiento con estos fármacos hasta mayo-2018 fuera de ensayo clínico. Se utilizó el parámetro supervivencia libre de progresión (SLP) para evaluar la efectividad, y la clasificación de la Common Terminology Criteria for Adverse Events y la ficha técnica para evaluar la seguridad.Resultados: Se analizó el tratamiento con daratumumab en 14 pacientes (media de 3,6 líneas de tratamiento previos y 5,1 ciclos de tratamiento) y el de carfilzomib en 21 pacientes (media de 3,1 líneas y 5,8 ciclos). La mediana de SLP observada fue de 4,8 meses para daratumumab y 5,8 meses para carfilzomib. Con daratumumab las reacciones adversas más frecuentes fueron trombocitopenia (50%), neutropenia (42,9%) y tos (42,9%), siendo las dos primeras las de mayor gravedad. Con carfilzomib, fueron anemia (95,2%), infección respiratoria (61,9%) y tos (61,9%), siendo trombocitopenia la más grave.Conclusiones: Daratumumab presenta una efectividad acorde a la literatura, pero inferior a la ficha técnica. Destaca la mayor incidencia de trombocitopenia, incluyendo casos graves. La efectividad de carfilzomib resulta inferior a la de ficha técnica, no siendo posible su comparación con otros estudios de práctica clínica. Se observa un peor perfil de seguridad, destacando la mayor incidencia de cardiotoxicidad y trombocitopenia en los casos más graves. Serán necesarios más estudios para dar solidez a estos hallazgos. (AU)

Objetives: The objective of the study is to evaluate the effectiveness and safety of daratumumab and carfilzomib in clinical practice, as well as to compare these results with the available literature and the fact sheet.Material and methods: Retrospective and observational study which patients were collected on treatment with these drugs until may-2018 out of clinical trial. The progression free survival (PFS) parameter was used to assess the effectiveness, and the classification of the Common Terminology Criteria for Adverse Events and fact sheet to the safety assessment.Outcomes: Treatment with daratumumab was analyzed in 14 patients (mean of 3.6 previous treatment lines and 5.1 treatment cycles) and the carfilzomib treatment in 21 patients (mean of 3.1 lines and 5.8 cycles). The median PFS observed was 4.8 months for daratumumab and 5.8 months for carfilzomib. The most common adverse reactions with daratumumab were thrombocytopenia (50%), neutropenia (42.9%) and cough (42.9%), the first two being the most serious. With carfilzomib, they were anemia (95.2%), respiratory infection (61.9%) and cough (61.9%), with thrombocytopenia being the most severe.Conclusion: Daratumumab has a literature consistent effectiveness but inferior to the fact sheet. It highlights the higher incidence of thrombocytopenia, including the most severe cases. The effectiveness of carfilzomib is lower than the fact sheet, and its comparison with clinical practice studies is not possible. A lower safety profile is observed, highlighting the higher incidence of cardiotoxicity and thrombocytopenia in the most severe cases. Further studies will be needed to give strength to these findings. (AU)

[Impact of a quality improvement plan on the validation of drug prescriptions on the safety of the hospitalised patient]. / Impacto de un plan de mejora de calidad en la validación de la prescripción de fármacos sobre la seguridad de los pacientes hospitalizados.

BACKGROUND AND OBJECTIVES: Medication errors are the most common adverse events in healthcare. Pharmaceutical validation (PV) seeks to reduce them. The aims of this study were to assess the impact of the introduction of an automated tool for the validation (VPAT) of the high clinical relevance drugs prescription (HCRD) over time of pharmaceutical intervention (PI), and to quantify the number of medication errors detected before and after its implementation. MATERIAL AND METHODS: A two phase retrospective-observational single centre study was designed. A pre-intervention phase (Pre-P): PV of beds with Unit Dose Dispensing (October 2015 - February 2016), was followed by a post-intervention phase (Post-P): PV using a VPAT of HCRD in hospital patients (October 2016 - February 2017). HCRD were selected from the list of high-risk drugs of Institute for Safe Medication Practices. The data was obtained from the PI record (Access®) and the computerised prescription. The variables collected were: age and gender of the patients included, data of drugs prescription, and time to PI. RESULTS: A total of 477 PI were analysed in 404 patients, with a mean age of 65.9±19.5 years (53.22% women). The mean time up to PI was 25.6±24.72h in the Pre-P, and 18.87±20.44h in the Post-P (P=0.01). In Pre-P, 106 PI were performed (35.85% prevention of adverse reactions) compared to 371 PI (39.62% medication reconciliation) in Post-P. CONCLUSIONS: The VPAT enabled a greater number of medication errors to be detected and intervened in hospitalised patients, with a significantly reduced time to PI.

Efectividad y seguridad de regorafenib y trifluridina/tipiracilo en cáncer colorrectal metastático / Effectiveness and safety of regorafenib versus trifluridine/tipiracil in metastatic colorectal cancer

OBJETIVOS: Comparar la efectividad y seguridad de regorafenib y trifluridina/tipiracilo en pacientes con cáncer de colon metastático en la práctica clínica real. MÉTODOS: Estudio retrospectivo observacional entre febrero 2013 y mayo 2017. Se incluyeron todos los pacientes con cáncer de colon metastático que empezaron tratamiento con regorafenib o trifluridina/tipiracilo. Se recogieron variables demográficas, diagnósticas y terapéuticas; y los efectos adversos y reducciones de dosis para evaluar la seguridad. La supervivencia global (SG) y supervivencia libre de progresión (SLP) se calcularon con el método de Kaplan-Meier, evaluándose las diferencias mediante la determinación del hazard ratio (HR) con un modelo de riesgo proporcional de Cox. RESULTADOS: Se incluyeron 39 pacientes (61,54% mujeres, edad media: 62,69 ± 11,51 años, 76,92% ECOG1, mediana de líneas de tratamiento previas 3,28 ± 1,02; 58,97% RAS mutado, 61,54% presentaban metástasis en el diagnóstico): 10 iniciaron regorafenib y 29 trifluridina/tipiracilo. La mediana de SLP fue 1,77 meses con regorafenib y 2,46 con trifluridina/tipiracilo (HR 1,35 (0,64-2,85), p = 0,428), y de SG 7,00 meses con ambos (HR 1,45 (0,68-3,09), p = 0,335). Las diferencias no fueron estadísticamente significativas. La media de efectos adversos por paciente fue 3,70 ± 2,35 con regorafenib y 2,55 ± 2,16 con trifluridina/tipiracilo, siendo los más frecuentes con regorafenib astenia, diarrea, síndrome mano-pie, hiporexia y mucositis; y con trifluridina/tipiracilo astenia, neutropenia y náuseas. El 30,00% de pacientes con regorafenib y el 27,58% con trifluridina/tipiracilo necesitaron reducir la dosis por toxicidad. CONCLUSIÓN: En nuestro estudio, regorafenib y trifluridina/tipiracilo tienen una efectividad similar y modesta. Los distintos perfiles de toxicidad de los fármacos deben tenerse en cuenta en la selección del tratamiento

PURPOSE: To compare effectiveness and safety of regorafenib and trifluridine/tipiracil in patients with metastatic colorectal cancer in real clinical practice. METHODS: A retrospective observational study including all patients with metastatic colorectal cancer who started treatment with regorafenib or trifluridine/ tipiracil (February 2013-May 2017) was carried out. Demographic, diagnostic and therapeutic variables were collected. Adverse effects and dose reductions were recorded to measure safety. Median progression free survival (PFS) and overall survival (OS) were recorded. Differences in survival were evaluated using the Cox's proportional hazard models to determine the hazard ratio. RESULTS: Throughout the period of the study 39 patients were included (61.54% women, median age 62.69 ± 11.51 years, 76.92% ECOG1, median previous lines 3.28 ± 1.02, 58.97% mutant RAS, 61.54% had metastasis in the diagnosis): 10 patients started treatment with regorafenib and 29 with trifluridine/tipiracil. The median PFS with regorafenib was 1.77 months and with trifluridine/tipiracil 2.46 months (HR 1.35 (0.64-2.85), p = 0.428), and the median OS was 7.00 months with both drugs (HR 1.45 (0.68-3.09), p = 0.335). Differences in survival were not statistically significant