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.

Ampicillin-resistant and vancomycin-susceptible Enterococcus faecium bacteremia: a clinical narrative review.

INTRODUCTION: Enterococcus faecium is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible E. faecium (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question. AREAS COVERED: This article mostly reviews the relevant aspects of EfARSV bacteremia: microbiology, gastrointestinal tract colonization and invasion, antibiotic resistance, epidemiology, risk factors, mortality, and treatment, including pharmacologic components of employed agents and related clinical evidence. A literature search was conducted on PubMed on 31 July 2022, which was updated on 15 November 2022. EXPERT OPINION: EfARSV bacteremia presents high mortality. However, it is uncertain whether mortality is attributable to or a marker of severity/comorbidities. Considering its antibiotic resistance pattern, EfARSV is considered a difficult-to-treat microorganism. Glycopeptides have been used to treat EfARSV, with linezolid and daptomycin serving as potential alternative agents. Yet, the use of daptomycin is controversial due to a higher risk of treatment failures. Clinical evidence on this issue is scarce, unfortunately, and subject to many limitations. Despite increased incidence and mortality, EfARSV bacteremia presents multiple aspects to be addressed in well-conducted studies.

Primary care electronic medication record discrepancies in patients starting treatment at a hospital-based ambulatory care pharmacy and impact on prevalence of potential drug-drug interactions.

OBJECTIVE: Our objective was to evaluate the prevalence of discrepancies between primary care electronic medication records (EMR) and patient reported medication (PRM) in ambulatory patients starting a hospital dispensing treatment (HDT) at a hospital-based ambulatory care pharmacy (HACPh). Our secondary aims were to analyse factors associated with the presence of discrepancies and their impact on the prevalence of potential drug-drug interactions (DDIs) with the HDT. METHODS: Retrospective study including 230 patients starting a HDT at the HACPh. Pharmacists interviewed patients and PRM was compared with EMR. Discrepancies were classified as omissions (medication in the PRM not present in the EMR) and commissions (medication active in the EMR that the patients were not taking). Potential DDIs with the HDT were screened, and univariate and multivariate analyses were performed to detect factors associated with the presence of discrepancies. RESULTS: We identified 221 discrepancies in 116 (50.4%) patients. Being visited by three or more medical specialties (OR 1.93, 95% CI 1.11 to 3.37) and attending private healthcare (OR 4.36, 95% CI 1.14 to 16.72) in the 12 months before the study inclusion were the factors independently associated with the presence of discrepancies. Among patients with commissions (n=91), 15.4% had a potential DDI between the HDT and one medication from the EMR that they were not taking at that moment. Among patients with omissions (n=45), 11.1% had a potential DDI between the HDT and a medication in the PRM not present in the EMR. CONCLUSIONS: About 40% of patients had one or more medications in the EMR which they were not taking and one fifth used medications that were not listed in the EMR. EMR should not be used as the only source of information when screening for DDIs, especially in patients followed by different medical specialties or combining private and public healthcare.

Treatment of non-metastatic castration-resistant prostate cancer: facing age-related comorbidities and drug-drug interactions.

INTRODUCTION: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) are frequently poly-medicated due to age-related and androgen deprivation therapy (ADT)-derived comorbidities. In high-risk patients, androgen receptor inhibitors (ARIs) have shown to delay disease progression; however, drug-drug interactions (DDIs) with preexisting medications may impact the therapeutic effect and safety of these and of the ARIs themselves. AREAS COVERED: We review the potential comorbidity burden of nmCRPC patients on the basis of epidemiologic studies on age-related comorbidities, the impact of ADT and specific studies analyzing this topic. Using the DDIs compendia Lexicomp® and Drugs.com®, we provide a scenario of the potential DDIs between common mediations used to treat these comorbidities and the three currently available ARIs: apalutamide, enzalutamide and darolutamide. EXPERT OPINION: In high-risk nmCRPC patients to be treated with an ARI, careful multidisciplinary evaluation of potential DDIs is a fundamental component in the clinical-decision making. The lower potential for DDIs, the lower need for dose adjustment or change of current comedications and of patient monitoring, and safer introduction of new comedications. To optimize this step, an effort is still needed to determine the clinical relevance of DDIs and to harmonize their definition and classification among the different compendia.

Prostate cancer is one of the most common cancers in men. It is normally diagnosed at age 60 or above, so these men are usually taking medications to treat age-related conditions (e.g. hypertension, diabetes, high cholesterol, etc.).One of the main treatments for prostate cancer is 'androgen deprivation therapy' (ADT), a hormone treatment that reduces androgens level. This is because the growth of prostate cancer cells is dependent on male sex hormones called androgens. Despite ADT helping keep the cancer controlled for a time, it increases the risk for adverse events that may need new medications. Consequently, men with prostate cancer usually take multiple medications.After some years, ADT may not be enough to control the prostate cancer. A type of medication called 'androgen receptor inhibitors' (ARIs), which prevent the androgen entering the cell, are helpful at this stage, especially the second-generation ones: apalutamide, enzalutamide, and darolutamide. The problem is that these ARIs usually interact with other medications already taken by patients, an effect called 'drug­drug interaction.' When this happens, the ARI (the interaction 'perpetrator') may modify the effectiveness of other medications (the 'victims') and/or cause unexpected effects. Consequently, the conditions being treated by these medications may not be properly controlled, which may pose a risk to the patient's health. Thus, when starting treatment with a second-generation ARI, it is crucial to consider all possible interactions with the medications taken. The fewer potential interactions the ARI has, the easier it is to properly control other common conditions in prostate cancer patients.

The correct knowledge of remdesivir management, includSuccessful management of remdesivir extravasation

No disponible

Impact of drug safety warnings and antimicrobial stewardship programme implementation on tigecycline prescribing: a prospective quasi-experimental interrupted time series analysis.

BACKGROUND: Tigecycline is the first member of the glycylcyclines. Both the FDA (2010 and 2013) and the EMA (2011) issued safety warnings describing an increased mortality risk associated with tigecycline compared with other antibiotics treating severe infections. One of the best strategies to optimize antimicrobial therapies is through the establishment of antimicrobial stewardship programmes (ASPs) in hospitals. In June 2011, our ASP was implemented. OBJECTIVES: To analyse trends in tigecycline prescription, after drug safety warning announcements by regulatory agencies and after an ASP implementation. METHODS: A 6 year prospective observational study of tigecycline use was performed, including all consecutive adult patients treated with at least one dose during the 6 years after approval of the drug for its use in the hospital. The primary outcome was tigecycline consumption assessed by DDD/100 bed-days. A segmented linear regression model for interrupted time series (ITS) was designed to detect any significant trend changes. RESULTS: A total of 524 patients were included. After the FDA warning alert, tigecycline consumption decreased by 35.9%. Moreover, following the ASP implementation, a dramatic reduction in tigecycline prescription by 67.3% was observed. CONCLUSIONS: The role of the ASP was essential to establish adequate control of prescriptions, collaborating with the clinicians in a better adaptation of the tigecycline indication.

Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review.

INTRODUCTION: Aspergillus may cause different types of lung infections: invasive, chronic pulmonary or allergic bronchopulmonary aspergillosis. Pharmacological management with antifungals poses as a challenge. Patients diagnosed with pulmonary aspergillosis are complex, as well as the problems associated with antifungal agents. AREAS COVERED: This article reviews the pharmacology of antifungal agents in development and currently used to treat pulmonary aspergillosis, including the mechanisms of action, pharmacokinetics, pharmacodynamics, dosing, therapeutic drug monitoring and safety. Recommendations to manage situations that arise in daily clinical practice are provided. A literature search of PubMed was conducted on November 15th, 2020 and updated on March 30th, 2021. EXPERT OPINION: Recent and relevant developments in the treatment of pulmonary aspergillosis have taken place. Novel antifungals with new mechanisms of action that extend antifungal spectrum and improve pharmacokinetic-related aspects, drug-drug interactions and safety are under current study. For those antifungals already marketed, new data related to pharmacokinetics, pharmacodynamics, dose adjustments in special situations, therapeutic drug monitoring and safety are available. To maximize efficacy and reduce the risk of associated toxicities, it is essential to choose the most appropriate antifungal; optimize its dose, interval, route of administration and length of treatment; and prevent side effects.

Clasificación del daño tisular de antineoplásicos: Consenso del Grupo Español de Farmacia Oncológica / Classification of antineoplastic drug-induced tissue damage: a Consensus of the Spanish Oncology Pharmacy Group

Objetivo: Realizar un consenso de expertos utilizando el método Delphipara la clasificación del potencial de daño tisular de los antineoplásicosque 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 comocoordinador. Se revisó la probabilidad de daño tisular a partir de ochodocumentos de referencia. Se clasificaron en cuatro categorías: vesicante, irritante de alto riesgo, irritante de bajo riesgo y no irritante. Serealizaron dos rondas; tras éstas los fármacos con consenso < 70% sediscutieron 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 declasificación entre los documentos consultados. Se utilizó el programaestadístico SPSS v23.0. (AU)

Objective: To reach at an expert consensus, using the Delphi method, forclassifying the tissue-damaging potential of antineoplastic drugs, in order tofacilitate 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 memberserved as coordinator. The likelihood of tissue damage was reviewed on thebasis 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 agreementof less than 70% after the two rounds were discussed non-anonymously by thegroup. For each of the rounds the following was analysed: median ofthe degree of consensus and the interquartile range (IQR25-75), degreeof agreement by tissue damage category, and percentage of antineoplastics reaching a degree of consensus of over 85% and of 100%. Drugswhose classification differed in the various reference documents were assessed separately. SPSS v23.0 statistical software was used. (AU)

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.

Eficacia y seguridad de una nueva formulación de enjuague bucal de dexametasona para el manejo de la estomatitis en pacientes con cáncer / Effectiveness and safety of a novel dexamethasone mouthwash formulation in managing stomatitis in cancer patients

OBJETIVO: Describir una nueva formulación de enjuague bucal con dexametasona y analizar su efectividad y seguridad en pacientes que reciben agentes antineoplásicos que producen estomatitis. MÉTODO: Estudio observacional prospectivo realizado en un hospital universitario entre marzo de 2017 y noviembre de 2019. Se incluyeron los pacientes que iniciaron everolimus. El tratamiento consistió en enjuagar con solución oral de dexametasona dos veces al día hasta la interrupción del tratamiento con everolimus. Se reclutó una segunda cohorte de pacientes con estomatitis inducida por otros agentes antineoplásicos con alta probabilidad de provocar estomatitis. Se evaluó la efectividad y seguridad del enjuague bucal con dexametasona. RESULTADOS: Se reclutaron nueve pacientes en profilaxis con formulación de enjuague bucal con dexametasona; seis pacientes presentaban un diagnóstico de cáncer de mama, dos de tumor neuroendocrino y uno de carcinoma renal. Cuatro pacientes desarrollaron estomatitis leve (grado 1-2) y tres pacientes descontinuaron everolimus por otros eventos adversos relacionados con el tratamiento. Se prescribió enjuague bucal con dexametasona en cinco pacientes con estomatitis existente como tratamiento. Todos los pacientes lograron una reducción significativa de la gravedad de la estomatitis tras iniciar el enjuague bucal con dexametasona. En general, el nuevo enjuague bucal con dexametasona fue bien tolerado y no se requirieron reducción de dosis ni interrupción debido a estomatitis. CONCLUSIONES: La nueva formulación de enjuague bucal con dexametasona podría considerarse una alternativa adecuada para el manejo de la estomatitis

OBJECTIVE: To present a new dexamethasone mouthwash formulation and analyze its effectiveness and safety among patients receiving stomatitis-producing antineoplastic agents. METHOD: Prospective observational study conducted in a university hospital between March 2017 and November 2019. Consecutive patients starting everolimus were enrolled. Patients were instructed to rinse dexamethasone mouthwash formulation twice daily until discontinuation of everolimus. A second cohort of patients with existing stomatitis induced by high probability of producing stomatitis chemotherapy therapies was also recruited to assess treatment effectiveness. Effectiveness and safety of dexamethasone mouthwash formulation was assessed. RESULTS: Dexamethasone mouthwash formulation was prescribed in nine patients as prophylaxis. Six patients were diagnosed with breast cancer, two with neuroendocrine tumor and one with renal cell carcinoma. Four patients developed mild stomatitis (grade 1-2) and three patients discontinued everolimus due to other treatment-related adverse events. In addition, dexamethasone mouthwash formulation was prescribed as treatment in five patients with existing stomatitis. All patients achieved a significant reduction in the severity of stomatitis after starting the dexamethasone mouthwash formulation. In both cohorts, dexamethasone mouthwash formulation was well tolerated and neither dose reduction nor discontinuation related to stomatitis was required. CONCLUSIONS: Dexamethasone mouthwash formulation could be considered as a suitable alternative for stomatitis management

Breast cancer, placing drug interactions in the spotlight: is polypharmacy the cause of everything?

Breast cancer is the most prevalent and lethal cancer among women. Forty-one percent of cases occur in people ≥ 70 years, hindering their treatment given its comorbidities and polypharmacy (PP). Potential drug–drug interactions (PDDI) were analyzed in elderly breast cancer patients between daily and oncospecific treatments and their associations with Age, BMI, Mini Nutritional Assessment (MNA), Frailty categorization, PP, and adverse effects. Patients/methods A cohort of 77 patients ≥ 70 years with breast cancer who underwent a Comprehensive Geriatric Assessment (CGA) were included. Clinical characteristics were collected using medical records. PDDI between treatments were analyzed using two databases. Data were assessed using linear regression, Chi-square, Mann–Whitney U, and Kruskal–Wallis tests. Finally, a multivariate logistic regression model was built and tested to predict adverse effects. Results From 719 PDDI, 530 (74%) were moderate (r2 = 0.72) and the median number of drugs during oncospecific treatment (r2 = 0.73) was 9 (range 3–26). Overall, 59 patients (77%) had adverse effects associated with Frailty categorization and MNA (p < 0.05). The distribution of major, moderate, minor, and total PDDI was associated with PP at CGA and during oncospecific treatment (p < 0.05). Moreover, it was verified that Frailty categorization protects from adverse effects given the intervention made at CGA. Conclusions CGA should be applied in oncologic elderly patients to assess clinical outcomes and categorize them according to their frailty but also to analyze PDDI. Furthermore, we encourage the use of the model in clinical practice for predicting the occurrence of adverse effects, improving therapeutic conciliation (AU)

Monoclonal antibody extravasations: Two case reports and literature review.

INTRODUCTION: Extravasation is a rare complication from intravenous chemotherapy administration. Literature about monoclonal antibody (MoAb) extravasations is scarce and also conflicting in how they are classified. CASE REPORT: We reported two different cases of MoAb extravasations with cetuximab and nivolumab outcome respectively. The administration site appeared inflamed and patients did not report disturbances.Management and outcome: Both extravasations did not require specific treatment. General unspecific measures suffice to properly manage these extravasations and no sequels were observed after long follow-up. Both patients received all further courses of MoAb without any adverse events. DISCUSSION: To our knowledge, we reported the first case-report of nivolumab extravasation in the literature. In addition, the cetuximab extravasation management and outcome was in accordance with previously published reports. Both MoAb may be considered as non-aggressive or neutral. We reviewed published information about MoAb extravasations. In conclusion, not all MoAb should be classified in the same category when extravasated and special precautions are warranted with conjugated MoAb and bevacizumab.

Breast cancer, placing drug interactions in the spotlight: is polypharmacy the cause of everything?

PURPOSE: Breast cancer is the most prevalent and lethal cancer among women. Forty-one percent of cases occur in people ≥ 70 years, hindering their treatment given its comorbidities and polypharmacy (PP). Potential drug-drug interactions (PDDI) were analyzed in elderly breast cancer patients between daily and oncospecific treatments and their associations with Age, BMI, Mini Nutritional Assessment (MNA), Frailty categorization, PP, and adverse effects. PATIENTS/METHODS: A cohort of 77 patients ≥ 70 years with breast cancer who underwent a Comprehensive Geriatric Assessment (CGA) were included. Clinical characteristics were collected using medical records. PDDI between treatments were analyzed using two databases. Data were assessed using linear regression, Chi-square, Mann-Whitney U, and Kruskal-Wallis tests. Finally, a multivariate logistic regression model was built and tested to predict adverse effects. RESULTS: From 719 PDDI, 530 (74%) were moderate (r2 = 0.72) and the median number of drugs during oncospecific treatment (r2 = 0.73) was 9 (range 3-26). Overall, 59 patients (77%) had adverse effects associated with Frailty categorization and MNA (p < 0.05). The distribution of major, moderate, minor, and total PDDI was associated with PP at CGA and during oncospecific treatment (p < 0.05). Moreover, it was verified that Frailty categorization protects from adverse effects given the intervention made at CGA. CONCLUSIONS: CGA should be applied in oncologic elderly patients to assess clinical outcomes and categorize them according to their frailty but also to analyze PDDI. Furthermore, we encourage the use of the model in clinical practice for predicting the occurrence of adverse effects, improving therapeutic conciliation.

Prognostic factors and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer treated with immune checkpoint blockage.

Our aim was to describe the incidence and characteristics of immune-related adverse events (irAEs) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and to evaluate their impact on outcome. All cases of NSCLC patients treated with ICIs in the second-line setting between December 2015 and May 2018 were evaluated. Seventy patients were included. Mean age was 65.9 years, and the majority of male (n = 53, 75.7%), with PS of 0-1 (n = 62, 88.6%) treated with nivolumab (n = 51; 72.9%). Thirty-one patients (44.3%) experienced an AE, 5 (7.1%) were grades 3-4. Median OS in patients with AE was 30.1 months (95% CI, 16.7-43.5) compared with 5.1 months (95% CI, 1.2-9.0) in cases without AE (log-rank test: p = 0.010). The adjusted HR for OS was 0.46 (95% CI, 0.25-0.86) for the irAE occurrence and 3.60 (95% CI, 1.56-8.32) for PS 2-3 group. The development of irAEs was associated with improved patient outcome.

Effectiveness and safety of a novel dexamethasone mouthwash formulation in managing stomatitis in cancer patients.

OBJECTIVE: To present a new dexamethasone mouthwash formulation and  analyze its effectiveness and safety among patients receiving stomatitis-producing antineoplastic agents. METHOD: Prospective observational study conducted in a university hospital between March 2017 and November 2019. Consecutive patients starting everolimus were enrolled. Patients were instructed to rinse dexamethasone mouthwash formulation twice daily until discontinuation of everolimus. A second cohort of patients with existing stomatitis induced by  high probability of producing stomatitis chemotherapy therapies was also  recruited to assess treatment effectiveness. Effectiveness and safety of dexamethasone mouthwash formulation was assessed. RESULTS: Dexamethasone mouthwash formulation was prescribed in nine patients as prophylaxis. Six patients were diagnosed with breast cancer, two with neuroendocrine tumor and one with renal cell carcinoma. Four patients developed mild stomatitis (grade 1-2) and three patients  discontinued everolimus due to other treatment-related adverse events. In  addition, dexamethasone mouthwash formulation was prescribed as treatment in five patients with existing stomatitis. All patients achieved a significant reduction in the severity of stomatitis after starting the  dexamethasone mouthwash formulation. In both cohorts, dexamethasone  mouthwash formulation was well tolerated and neither dose reduction nor  discontinuation related to stomatitis was required. CONCLUSIONS: Dexamethasone mouthwash formulation could be considered as a  suitable alternative for stomatitis management.

Objetivo: Describir una nueva formulación de enjuague bucal con dexametasona y analizar su efectividad y seguridad en pacientes que reciben agentes antineoplásicos que producen estomatitis.Método: Estudio observacional prospectivo realizado en un hospital universitario entre marzo de 2017 y noviembre de 2019. Se incluyeron los pacientes que  iniciaron everolimus. El tratamiento consistió en enjuagar con solución oral de  dexametasona dos veces al día hasta la interrupción del tratamiento con  everolimus. Se reclutó una segunda cohorte de pacientes con estomatitis  inducida por otros agentes antineoplásicos con alta probabilidad de provocar  estomatitis. Se evaluó la efectividad y seguridad del enjuague bucal con  dexametasona.Resultados: Se reclutaron nueve pacientes en profilaxis con formulación de  enjuague bucal con dexametasona; seis pacientes presentaban un diagnóstico  de cáncer de mama, dos de tumor neuroendocrino y uno de carcinoma renal.  Cuatro pacientes desarrollaron estomatitis leve (grado 1-2) y tres pacientes  descontinuaron everolimus por otros eventos adversos relacionados con el  tratamiento. Se prescribió enjuague bucal con dexametasona en cinco pacientes  con estomatitis existente como tratamiento. Todos los pacientes lograron una  reducción significativa de la gravedad de la estomatitis tras iniciar el enjuague  bucal con dexametasona. En general, el nuevo enjuague bucal con  dexametasona fue bien tolerado y no se requirieron reducción de dosis ni  interrupción debido a estomatitis.Conclusiones: La nueva formulación de enjuague bucal con dexametasona podría considerarse una alternativa adecuada para el manejo de la estomatitis.

Hypersensitivity reaction caused by folinic acid administration: a case report and literature review.

5-Fluorouracil (5-FU) is combined with folinic acid (FA) for enhancing its cytotoxic effects in the colon cancer chemotherapy treatment. Folinic acid has rarely been involved in hypersensitivity reactions. Here, we report a case of FA hypersensitivity in an adult patient initially attributed to oxaliplatin administered concurrently. A 56-year-old male patient diagnosed with colon cancer received twelve cycles of FOLFOX4, one cycle of FOLFIRI plus cetuximab and nine cycles of FOLFOX6 uneventful. At the tenth cycle of FOLFOX6 chemotherapy, after 15 minutes of starting the infusion of oxaliplatin and FA, the patient reported flushing, pruritus and abdominal pain and erythema and oedema developed over the face and thorax. After progression, FOLFIRI plus aflibercept was scheduled and another reaction occurred. At this time, FA was discontinued and the patient received another cycle consisted on irinotecan plus 5-FU without incidences. This episode of hypersensitivity reaction following FA infusion with no oxaliplatin empirically confirmed that the hypersensitivity reaction was secondary to FA. Clinicians should be aware of hypersensitivity reaction with FA, especially when FA is administered concomitantly with oxaliplatin, despite its lower risk to cause hypersensitivity reactions. Furthermore, the similar signs and symptoms associated to the hypersensitivity reactions of each agent, highlight the importance of having a specialised allergist team for to make a prompt diagnose of the causative agent in order to prevent patient harm and proceed properly without unnecessary delays in the scheduled chemotherapy treatments.

An overview of randomized clinical trials in metastatic breast cancer: variables affecting regulatory drug approval.

The aim of this study was to analyse trial variables affecting drug approval in metastatic breast cancer (MBC). A literature search from 2000 to 2012 retrieved 66 phase III randomized controlled trials with reported primary endpoints in MBC and known outcomes in terms of approval. The influence of the primary endpoint, the line of therapy, crossover and the sample size was analysed. The primary endpoints used most frequently were progression-free survival (PFS) and time to progression or time to treatment failure (N=47; 71%). Overall survival (OS) was a primary endpoint in nine trials (14%). In 26 trials (39%), statistically significant results were found with respect to the primary endpoint, and in 13 trials (20%), this was found with respect to the secondary endpoint. Gains in OS were found in 12 trials (18%), whereas a benefit to PFS was found in 30 trials (46%). The average median OS was 23.1 months. Postprogression survival accounted for 64% of OS. Trials with crossover did not have OS as the primary endpoint. Trials that resulted in drug approval had a more pronounced gain in OS or PFS and had more patients than those without regulatory consequences. PFS was the main primary endpoint in randomized clinical trials in MBC and was significantly associated with drug approval. OS benefit was rarely achieved in trials where this was not the primary endpoint. The number of randomized patients, the primary endpoint and crossover are factors linked to regulatory requirements for approval, which should be considered in future trial designs.