Uso compasivo de durvalumab en cáncer de pulmón no microcítico: resultados en vida real / Compassionate use of durvalumab in non-small cell lung cáncer: real-life results

Objetivos: Durvalumab está financiado en cáncer de pulmón no microcítico (CPNM) localmente avanzado irresecable con expresión PD-L1 ≥1%, sin progresión tras quimiorradioterapia basada en platino y duración del tratamiento de 12 meses. Los pacientes deben presentar buen estado general (PS). Hasta ahora, sólo el uso compasivo ha sido autorizado, sin algunos requisitos de financiación exigidos. El objetivo es describir las condiciones del uso compasivo de durvalumab en CPNM, comparándose con las condiciones de financiación, así como proporcionar resultados en vida real de efectividad y seguridad.Métodos: Se desarrolló un estudio descriptivo retrospectivo entre 01/12/2017-29/02/2020. La efectividad se evaluó con supervivencia global (SG) y supervivencia libre de progresión (SLP) mediante método Kaplan Meier utilizando SPSS Statistics®. La seguridad se evaluó con reacciones adversas (RAs), grado, interrupciones y suspensiones.Resultados: Fueron reclutados 5 pacientes. Se determinó PD-L1 ≥1% en uno. El 80% presentaron PS0. La mediana de seguimiento fue 19 (7-25) meses. Uno de los pacientes (20%) cumplió criterios de financiación. No se registraron fallecimientos, no pudiéndose estimar la media de SG. La media de SLP fue 20,8 (13,6-28,1) meses. Se observaron 17 episodios de RAs, siendo las más frecuentes: 4 (23,5%) infecciones respiratorias, 3 (17,6%) tos y 2 (11,7%) lesiones eritematosas. Se notificaron 16 (94,1%) RAs grado 1, y 8 interrupciones de tratamiento, sin suspensiones.Conclusiones: Existen importantes discrepancias entre el uso compasivo de durvalumab en CPNM localmente avanzado irresecable y las condiciones de financiación. Durvalumab ha demostrado importante efectividad y tolerancia aceptable, aunque estos resultados deben evaluarse con cautela. (AU)

Objectives: Durvalumab is funded in unresectable locally advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥1%, without progression after platinum-based chemoradiotherapy and treatment duration of 12 months. Patients must present adequate performance status (PS). Until now, only compassionate use has been authorized, without some funding requirements. The aim is to describe conditions of compassionate use of durvalumab in locally advanced and unresectable NSCLC, comparing with the financing conditions, as well as to provide the real-life results of effectiveness and security.Methods: A retrospective descriptive study from 01/12/2017 to 29/02/2020 was conducted. The effectiveness was assessed with overall survival (OS) and progression-free survival (PFS) by Kaplan Meier method using SPSS Statistics®. Safety was evaluated through adverse reactions (ARs), grade, interruptions and suspensions.Results: There were 5 male patients recruited. PD-L1 was ≥1% in one patient. The 80% of patients presented PS0. The median follow-up was 19 (7-25) months. One of the patients (20%) met the funding criteria. There were no deaths, so the mean OS could not be calculated. The mean PFS was 20.8 (13.6-28.1) months. There were 17 RAs episodes. The most frequent RAs were: 4 (23.5%) respiratory infections, 3 (17.6%) cough and 2 (11.7%) erythematous lesions. There were 16 (94.1%) RAs grade 1, and 8 treatment interruptions were recorded, without suspensions.Conclusions: There are important discrepancies between the compassionate use of durvalumab in unresectable locally advanced NSCLC and the financing conditions. Durvalumab has showed an important effectiveness and aceptable tolerance, although these results should be evaluated with caution. (AU)

Mitochondrial Complex I Inhibition by Metformin: Drug-Exercise Interactions.

Metformin has antidiabetic, anticancer, and prolongevity effects, but seems to interfere with aerobic training mitochondrial adaptations. The primary mechanism of action has been suggested to be the inhibition of mitochondrial complex I. Recent papers (Wang et al. and Cameron et al.), however, provide evidence to deny the hypothesis of a direct action of metformin on complex I.

Identification of a novel HLA-B*50 allele, HLA-B*50:01:08, in a Spanish hematological patient.

HLA-B*50:01:08 differs from B*50:01:01 at nucleotides g.1206T>A (intron 3) and g.1658G>A (exon 4).

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

BACKGROUND: Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. METHODS: ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. RESULTS: SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. CONCLUSION: ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE.

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