GEDEFO-SEFH management of antineoplastic extravasations survey results.

INTRODUCTION: Extravasation is a potentially severe complication of intravenous administration of antineoplastic drugs. The limited data makes it difficult to develop an optimal management scheme. The objective of this study is to describe the clinical practice in the extravasation management of antineoplastic agents in Spanish centers. METHODS: An online survey was distributed to oncology pharmacists using the email distribution list of the Spanish Society of Hospital Pharmacists. Respondents were surveyed on the standard operational protocol (SOP) of extravasation, tissue damage risk classification, and specific measures of extravasation management. RESULTS: A total of 68 surveys were completed. A specific extravasation SOP was available in 82.4% centers. The pharmacist participates in the authorship (100%) and actively collaborates in extravasation management (76.5%). A tissue damage risk classification based on the three categories was mostly adopted (48.2%) and 73.2% applied specific criteria based on concentration and/or extravasated volume. Extravasation management was mainly performed with the application of physical measures and/or antidotes (91.2%). High variability in the choices of pharmacological and/or physical measures recommended is outstanding. CONCLUSION: The results of this study highlight the involvement of Spanish pharmacists in extravasation management, the application of physical measures and/or pharmacological measures as the method of choice in extravasation management, as well as the existing discrepancies in tissue damage risk classification and management recommendations.

Cost-effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy in the maintenance of patients with homologous recombination deficiency-positive advanced ovarian cancer after response to first-line platinum-based chemotherapy.

OBJECTIVE: The PAOLA-1 trial confirmed that adding olaparib to bevacizumab significantly increased clinical benefit following response to platinum-based chemotherapy in homologous recombination deficiency-positive ovarian cancer. The objective of this analysis was to determine the cost-effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as maintenance treatment for patients with homologous recombination deficiency-positive advanced ovarian cancer from the Spanish National Health System perspective. METHODS: A lifetime partitioned survival model with four health states (progression-free, post-progression 1, post-progression 2, and death) and monthly cycles was developed. Long-term survival, defined as 60 months, was included as a landmark to extrapolate progression-free survival from PAOLA-1. Weibull distribution was selected as the most accurate survival model for progression-free survival extrapolation. Time to second progression and overall survival were extrapolated using parametric survival models. Mortality was obtained from the overall survival and adjusted by Spanish women mortality rates. Health state utilities and utility decrements for adverse events were included. An expert panel validated data and assumptions. Direct costs (in 2021 euros (€)) were obtained from local sources and included drug acquisition and administration, subsequent therapies, monitoring costs, adverse events, and palliative care. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio was calculated as cost per quality-adjusted life-years (QALYs) gained. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Compared with bevacizumab alone, olaparib plus bevacizumab increased QALYs and life-years by 2.39 and 2.77, respectively, at an incremental cost of €58 295.31, resulting in an incremental cost-effectiveness ratio of €24 371/QALY. Probabilistic sensitivity analysis demonstrated that olaparib plus bevacizumab had a 49.5% and 90.3% probability of being cost-effective versus bevacizumab alone at a willingness-to-pay threshold of €25 000 and €60 000 per QALY gained, respectively. CONCLUSION: For patients with homologous recombination deficiency-positive advanced ovarian cancer, olaparib plus bevacizumab is a cost-effective maintenance therapy compared with bevacizumab alone in Spain.

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness.

OBJECTIVE: To study immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab, as well as to assess whether these reactions could be predictors of further effectiveness of therapy. METHODS: Retrospective, observational and longitudinal study. All NSCLC patients who received nivolumab between February 2015-May 2020 were included. In terms of safety, irAEs and their severity were registered and to evaluate the effectiveness, overall survival (OS) and progression free survival (PFS) were calculated. RESULTS: 75 patients were included. 32 patients (43%) were reported irAES. Mainly the irAEs affected the skin (36%). Followed by pneumonitis (20%), gastrointestinal reactions (12%), endocrine (12%) and hepatitis (12%). Regarding severity, 92% were moderate. The median PFS was 9.49 months on the group with irAEs versus 1.99 months on the group without irAEs group (p < 0.0001). The median OS was 17.44 months versus 7.67 months respectively (p = 0.0001). According to the incidence of irAEs developed ( = > 2 vs. 1 vs. 0), the median PFS was 20.53 versus 5.35 versus 1.99 months respectively (p < 0.0001). The median OS was 23.41 versus 15.80 versus 7.67 months, respectively (p = 0.0002). CONCLUSION: In a significant number of patients irAEs occur, generally of grade 1-2 severity, affecting mainly the skin, lungs and gastrointestinal system. We confirm that the development of irAEs in patients with NSCLC treated with nivolumab is a strong predictor of treatment effectiveness in both PFS and OS, with statistically significant results. On those patients who experience two or more immunorelated adverse events the greatest benefit has been observed.

Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence.

INTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.

Classification of antineoplastic drug-induced tissue damage: a Consensus of the Spanish Oncology Pharmacy Group.

OBJECTIVE: To reach at an expert consensus, using the Delphi method, for classifying the tissue-damaging potential of antineoplastic drugs, in  order to facilitate the decision-making process in the event of  extravasations. METHOD: The panel of expert evaluators was made up of seven  pharmacists belonging to the working group on extravasations. Other  member served as coordinator. The likelihood of tissue damage was  reviewed on the basis of eight reference documents. Four categories of  drugs were established: vesicant (V); high risk irritant (HRI); low risk  irritant (LRI) and non-irritant (NI). Two rounds of surveys were performed. The drugs with an agreement of less than 70% after the two rounds were  discussed non-anonymously by the group. For each of the rounds the  following was analysed: median of the degree of consensus and the  interquartile range (IQR25-75), degree of agreement by tissue damage  category, and percentage of antineoplastics reaching a degree of  consensus of over 85% and of 100%. Drugs whose classification differed in the various reference documents were assessed separately. SPSS v23.0  statistical software was used. RESULTS: Seventy-one antineoplastics were evaluated. In the first round, the median for degree of consensus was 100.0% (IQR25-75: 71.4- 100.0%). In the second round, the median was 100.0% (IQR25-75: 85.7- 100.0%). The percentage of antineoplastics with a consensus of 85.7% or  above increased from 66.7% to 85.9% in the second round. For the 30  antineoplastics whose values differed in the reference documents, the  degree of agreement increased from 71.4% (IQR25-75: 57.1-87.7%) to  100.0% (IQR25-75: 85.7-100.0%) in the second round. The percentage of antineoplastics with a consensus of 85.7% or above increased from 40.0%  to 76.7%. Four antineoplastics had a degree of agreement of less  than 70.0%. The final classification of drugs per category, was: 17  vesicants; 15 HRI; 13 LRI; and 26 NI. The final degree of consensus was  85.7% or above for 90.1% of antineoplastics, and 100.0% for 74.6% of  the same. CONCLUSIONS: In this area of scarce evidence and high variability, the Delphi method allows for consensus in classifying tissue damage risk,  thus making it easier to reach clinical decisions. In approximately 90% of  the antineoplastics, the degree of consensus reached by the expert panel  was 85% or above. In 74% of the antineoplastics, it was 100%. This  provides solid ground for management decisions.

Objetivo: Realizar un consenso de expertos utilizando el método Delphi para la clasificación del potencial de daño tisular de los  antineoplásicos que facilite la toma de decisiones ante una extravasación.Método: El panel de evaluadores estaba formado por siete farmacéuticos del grupo de trabajo de extravasaciones. Otro actuó como coordinador. Se revisó la probabilidad de daño tisular a partir de  ocho documentos de referencia. Se clasificaron en cuatro categorías:  vesicante, irritante de alto riesgo, irritante de bajo riesgo y no irritante. Se realizaron dos rondas; tras éstas los fármacos con consenso < 70% se discutieron en grupo de forma no anónima. Se analizó para cada ronda: la mediana del grado de consenso y ámbito intercuartílico (AIQ25- 75), el grado de concordancia por categoría de daño tisular y el porcentaje de antineoplásicos con grado de consenso > 85% y del 100%. Se analizaron de forma separada los fármacos con discordancias de clasificación entre los documentos consultados. Se utilizó el programa estadístico SPSS v23.0.Resultados: Se evaluaron 71 antineoplásicos. En la primera ronda la mediana del grado de consenso fue 100% (AIQ25-75: 71,4-100,0%) y  en la segunda ronda 100% (AIQ25-75: 85,7-100,0%). El porcentaje de  antineoplásicos con consenso ≥ 85,7% aumentó del 66,7% al 85,9% en la segunda ronda. Para los 30 antineoplásicos con discrepancias entre los  documentos revisados, el grado de consenso aumentó del 71,4% (AIQ25- 75: 57,1-87,7%) al 100% (AIQ25-75: 85,7-100,0%) en la segunda ronda. El porcentaje de antineoplásicos con concordancia ≥ 85,7% pasó del  40,0% al 76,7%. Cuatro antineoplásicos presentaron consenso < 70%. La  clasificación final incluyó 17 fármacos como vesicantes, 15 como irritantes  de alto riesgo, 13 como irritantes de bajo riesgo y 26 como no irritantes. El grado de acuerdo final fue ≥ 85,7% en el 90,1% de los antineoplásicos y  del 100% en el 74,6%.Conclusiones: En este área de escasa evidencia y variabilidad la metodología Delphi permite alcanzar un consenso de clasificación del riesgo de daño tisular que facilita la toma de decisiones.  Aproximadamente para el 90% de los antineoplásicos el grado de  concordancia alcanzado por el panel de expertos fue > 85%, y para el  74% de los antineoplásicos la concordancia fue del 100%, aportando una  base sólida para las decisiones de manejo.

Monitoring contamination of hazardous drug compounding surfaces at hospital pharmacy departments. A consensus Statement. Practice guidelines of the Spanish Society of Hospital Pharmacists (SEFH).

OBJECTIVE: To establish a series of recommendations based on available evidence for monitoring surface contamination in the areas devoted to compounding hazardous drugs in pharmacy departments. METHOD: Based on a literature search in the Medline and Embase databases (search period: January 2009 to July 2019), as well as on a review of standards and recommendations issued by different healthcare organizations, a committee of experts from the Spanish Society of Hospital Pharmacists defined a series of safe practices for handling hazardous drugs and monitoring compounding work surfaces. Recommendation decisions were adopted by consensus among the members of the expert group, considering the recommendations reviewed, the monitoring situation in Spanish hospital departments, and the associated costs. RESULTS: Ten recommendations were formulated, structured into eight sections. They include aspects related to the drugs to be monitored; the  areas to be monitored; when samples should be taken; risk determination and preparation of a sampling protocol; analytical techniques; contamination thresholds; and design of an action plan based on the sampling and decontamination results obtained. CONCLUSIONS: Surface monitoring allows hazardous drugs detection and evaluation of the effectiveness of current protocols for the safe handling of such drugs in hospital pharmacy departments. The evaluation should include an analysis of the efficacy of engineering controls, work practices and cleaning and decontamination processes.

Objetivo: Establecer unas recomendaciones, en base a la evidencia disponible, para la monitorización de la contaminación de superficies en las áreas de elaboración de medicamentos peligrosos de los Servicios de Farmacia.Método:A partir de una revisión bibliográfica en las bases de datos Medline y Embase desde enero de 2009 a julio de 2019, así como de la consulta de documentos de estándares y recomendaciones de organizaciones sanitarias, un comité de expertos de la Sociedad Española de Farmacia Hospitalaria ha definido una serie de prácticas seguras sobre manipulación de medicamentos peligrosos y monitorización de superficies de trabajo. Las decisiones de recomendación se tomaron por consenso entre el grupo de expertos teniendo en cuenta las recomendaciones encontradas, la situación en nuestro entorno y los costes asociados a la monitorización.Resultados: Se han definido 10 recomendaciones estructuradas en ocho secciones. Se incluyen aspectos relacionados con los medicamentos a  monitorizar; localizaciones a monitorizar; momento de la toma de muestras; determinación del riesgo y plan de muestreo; técnicas analíticas; umbrales de contaminación; plan de acción según los resultados del muestreo y descontaminación.Conclusiones: La monitorización de superficies permite determinar la presencia de medicamentos peligrosos y evaluar la eficacia del programa de manejo seguro de los mismos en los Servicios de Farmacia. La  evaluación debería incluir un estudio de la eficacia de los controles de  ingeniería, de las prácticas laborales y de los procesos de limpieza y descontaminación.