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BACKGROUND: EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and effect of depleting EGF in moderate-to-severe COPD patients, with an EGF-based vaccine. PATIENTS AND METHODS: A phase I trial was conducted in subjects with moderate or severe COPD. The anti-EGF vaccine schedule consisted of 4 biweekly doses followed by 4 monthly boosters. The primary endpoint was the evaluation of the safety and immunogenicity of the vaccine, together with the change in FEV1 and physical function at week 24. RESULTS: Twenty-six patients with moderate or severe COPD were included in the trial. The vaccine was well tolerated and no serious related adverse events were reported. Ninety percent of the individuals developed a protective antibody response. The specific anti-EGF antibodies had high avidity and were able to inhibit EGFR phosphorylation. At the end of vaccination, serum EGF became undetectable. At week 24, there was a clinically significant improvement in lung function, with a mean change in trough FEV1 of 106 mL. Patients also increased their physical functioning. CONCLUSIONS: The EGF-based vaccine was immunogenic and provoked an EGF exhaustion in patients with moderate-to-severe COPD. Depleting EGF might result in a meaningful increase in FEV1, with good tolerability. The current results provide new avenues to treat chronic inflammatory lung diseases associated with EGFR aberrant signaling.
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The convergence of life sciences with neurosciences, nanotechnology, data management, and engineering has caused a technological diversification of the biotechnology, pharmaceutical, and medical technology industries, including the phenomenon of digital transformation, which has given rise to the so-called Fourth Industrial Revolution (Industry 4.0). Confronting the COVID-19 pandemic revealed the outstanding response capacity of the scientific community and the biopharmaceutical industry, based on a multidisciplinary and interinstitutional approach that has achieved an unprecedented integration in the history of biomedical science. Cuba, a small country, with scarce material resources, has had remarkable success in controlling the disease, which also highlights the impact of social factors. This report presents a summary of the most relevant presentations of selected topics during the scientific meeting, "BioHabana 2022: Cancer Immunotherapy and the COVID-19 Pandemic," which was held in Havana Cuba in April 2022.
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COVID-19 , Neoplasias , Humanos , Cuba , Pandemias/prevención & control , Neoplasias/prevención & control , InmunoterapiaRESUMEN
Introducción: La respuesta a las terapias en el cáncer de pulmón avanzado pudiera estar relacionada con determinados factores pronósticos como los índices inflamatorios. Objetivo: Evaluar la eficacia del anticuerpo monoclonal humanizado nimotuzumab en pacientes portadores de cáncer de pulmón no microcítico avanzado según índices inflamatorios. Método: Se realizó un estudio de evaluación longitudinal retrospectivo, en un universo de 498 pacientes mayores de 18 años, con diagnóstico citohistológico de cáncer de pulmón de células no pequeñas, en estadios avanzados, después de la primera línea de terapia oncológica, incluidos en ensayos clínicos multicéntricos promovidos por el Centro de Inmunología Molecular desde 2002 a 2018. Se aplicó la estadística descriptiva, se utilizó el software x-tile 3.6.1 para el test de Kaplan Meier; se consideraron diferencias significativas cuando p< 0,05. Resultados: En los pacientes analizados el nimotuzumab mostró beneficio terapéutico en el grupo de pacientes no progresores a la primera línea de tratamiento con quimioterapia o quimiorradioterapia, cuando tenían menor índice de neutrófilos/linfocitos (p= 0,017 y p= 0,027) y menor índice de plaquetas/linfocitos (p= 0,030 y p= 0,009). Conclusión: La selección de un paciente con menor índice inflamatorio beneficia la eficacia del tratamiento con el AcM humanizado nimotuzumab en el cáncer de pulmón avanzado no microcítico, la que se convierte en una herramienta predictiva de la respuesta al tratamiento(AU)
Introduction: The response to therapies in advanced lung cancer could be related to certain prognostic factors such as inflammatory indices. Objective: To evaluate the efficacy of the humanized monoclonal antibody nimotuzumab in patients with advanced non-small cell lung cancer according to inflammatory indices. Method: A retrospective longitudinal evaluation study was carried out in a universe of 498 patients older than 18 years, with a cytohistological diagnosis of non-small cell lung cancer, in advanced stages, after the first line of oncological therapy, including in multicenter clinical trials promoted by the Center for Molecular Immunology from 2002 to 2018. Descriptive statistics were applied, the x-tile 3.6.1 software was used for the Kaplan Meier test, significant differences were considered when p< 0,05. Results: In the patients analyzed, nimotuzumab showed therapeutic benefit in the group of patients who did not progress to the first line of treatment with chemotherapy or chemoradiotherapy, when they had a lower neutrophil-lymphocyte index (p= 0,017 and p= 0,027) and a lower platelet-lymphocyte index (p= 0,030 and p= 0,009). Conclusion: Selecting a patient with a lower inflammatory index benefits the efficacy of treatment with the humanized mAb nimotuzumab in advanced non-small cell lung cancer, which becomes a predictive tool for response to treatment(AU)
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Humanos , Adolescente , Pronóstico , Resultado del Tratamiento , Carcinoma de Pulmón de Células no Pequeñas/ultraestructura , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Pulmonares/terapia , Estudios Retrospectivos , Estudios Longitudinales , Estudio de EvaluaciónRESUMEN
In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients' burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. Clinical trial registration: https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.
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BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.
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Eritropoyetina , Ataxias Espinocerebelosas , Método Doble Ciego , Epoetina alfa , Eritropoyetina/uso terapéutico , Estudios de Factibilidad , Humanos , Proteínas Recombinantes/uso terapéutico , Ataxias Espinocerebelosas/tratamiento farmacológicoRESUMEN
Este reporte corresponde al análisis de la calidad de vida de los pacientes que se incluyeron en el ensayo clínico fase III de evaluación de la vacuna CIMAvaxEGF® en cáncer de pulmón de células no pequeñas. La calidad de vida se evaluó empleando los cuestionarios EORTC QLQ-C30 y QLQ-C13, al inicio y cada 3 meses hasta el fallecimiento del paciente a criterio del investigador. Para comparar las medianas entre los dos grupos se utilizó la prueba no paramétrica de Mann-Whitney. Las comparaciones entre el nivel basal y los diferentes tiempos de seguimiento se realizaron a través de la prueba no paramétrica de Wilcoxon. El cuestionario QLQ-C30 evidenció un beneficio en cuanto a calidad de vida para el grupo vacunado con la vacuna CIMAvaxEGF® en las escalas funcionales (global, rol y social), en las escalas de síntomas de la enfermedad y del tratamiento (dolor) se observó que mejora la calidad de los mismos a favor de los pacientes tratados con la vacuna CIMAvaxEGF®. El cuestionario QLQ-C13, también evidenció ventajas para el grupo vacunado desde el punto de vista de beneficio clínico en los síntomas (disnea, disfagia, alopecia y dolor en el pecho). Se señala como significativo que disminuye la hemoptisis y la tos en el grupo vacunado, observándose un empeoramiento en el grupo control(AU)
This report corresponds to quality of life analysis of patient with non-small cell lung cancer included in the phase III clinical trials Evaluation of CIMAvaxEGF® vaccine in lung cancer. The quality of life was evaluate using the EORTC questionnaires QLQ-C30 y QLQ-C13, at the beginning and every 3 months. To compare the median between two groups the Mann-Whitney non-parametric test was used. To compare the baseline and different follows times the Wilcoxon non-parametric test was used. The QLQ-C30 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the functional scores (global, role and social) and symptoms of the disease (pain). The QLQ-LC13 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the symptoms scores (dyspnea, dysphagia, alopecia and chest pain). It is noted as significant that the hemoptysis decreases in the group vaccinated as well as the dysphagia, the cough and the dyspnea observing a worsening in the control group(AU)
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Humanos , Masculino , Femenino , Calidad de Vida , Encuestas y Cuestionarios , Ensayos Clínicos Fase III como Asunto , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Vacunas contra el CáncerRESUMEN
Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors' sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.
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COVID-19/complicaciones , Fibrinolíticos/uso terapéutico , Arteria Pulmonar , Venas Pulmonares , SARS-CoV-2 , Estreptoquinasa/uso terapéutico , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/sangre , COVID-19/terapia , Coinfección , Terapia Combinada , Femenino , Hemorragia/inducido químicamente , Humanos , Hipoxia/etiología , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/terapia , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/terapia , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Respiración Artificial , Estreptoquinasa/efectos adversos , Trombofilia/etiología , Trombosis/etiologíaRESUMEN
EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate affinity anti-EGFR antibody, that apart from other drugs in its class, is very safe and does not cause hypomagnesemia or grade 3-4 cutaneous rash. The antibody inhibits cell proliferation and angiogenesis, activates natural killer cells, stimulates dendritic cell maturation, and induces cytotoxic T cells. Nimotuzumab restores MHC-I expression on tumor cells, hindering one of the EGFR immune-escape ways. The antibody has been extensively studied in 7 clinical trials, concurrently with irradiation or irradiation plus chemotherapy in subjects with inoperable head and neck tumors. Nimotuzumab was safe and efficacious in unfit patients receiving irradiation alone and in subjects treated with cisplatin and radiotherapy. In patients with locally advanced squamous cell carcinomas of the head and neck, nimotuzumab in combination with low dose cisplatin and radiotherapy was superior to cisplatin and radiotherapy in progression free survival, disease free survival, and locoregional tumor control.
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Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.
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Antineoplásicos/uso terapéutico , Vacunas contra el Cáncer/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Factor de Crecimiento Epidérmico/genética , Receptores ErbB/inmunología , Neoplasias Pulmonares/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Cetuximab/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Humanos , Inmunoterapia Activa , Neoplasias Pulmonares/terapia , Fosforilación , VacunaciónRESUMEN
INTRODUCCIÓN: con el empleo de anticuerpos monoclonales anti-receptor del factor de crecimiento epidérmico (EGFR), se reportan efectos adversos, entre ellos hipomagnesemia e hipocalcemia. El nimotuzumab, anti-EGFR de producción nacional, tiene otras particularidades en su mecanismo de acción. OBJETIVO: analizar si la administración de este fármaco causa hipomagnesemia e hipocalcemia secundaria, como el resto de los anti-EGFR. MÉTODOS: los pacientes del estudio provienen del ensayo clínico controlado: Uso del anticuerpo monoclonal nimotuzumab en el tratamiento de pacientes con carcinoma de células escamosas de cabeza y cuello, en estadios avanzados. De cada uno de los dos grupos de tratamiento del ensayo fueron seleccionados, mediante muestreo simple aleatorio, 12 pacientes. Se registraron las variables demográficas y antropométricas; se realizaron las determinaciones de calcio y magnesio, utilizando muestras de suero obtenidas durante el ensayo clínico y conservadas a 86 °C. La información fue procesada automatizada; paquete estadístico SPSS 15.0. Para determinar cambios en las concentraciones de Ca y Mg se utilizaron, respectivamente, los test de Friedman y de rangos con signos de Wilcoxon. En la comparación entre grupos se empleó el test de Wilcoxon-Mann-Whitney. RESULTADOS: los dos grupos de sujetos mostraron características semejantes. En el grupo tratado con nimotuzumab, las medias de las concentraciones de Mg fueron de 2,06; 2,17 y 2,11 mg/dL, al inicio, a las 3 sem y al final del tratamiento (p= 0,72). No existieron diferencias al comparar los cambios en las concentraciones de Mg y Ca entre ambos grupos (p= 0,07 y p= 0,86). CONCLUSIÓN: no existen evidencias para plantear que el nimotuzumab produzca hipomagnesemia e hipocalcemia secundarias, en cursos de tratamiento de 200 mg semanales por 6 sem.
INTRODUCTION: some adverse effects have been reported with the use of monoclonal antibodies against Epidermal Growth Factor Receptor (EGFR), including hypomagnesaemia and hypocalcaemia. Nimotuzumab is a Cuban anti-EGFR antibody with a particular mechanism of action, so it is important to know if Nimotuzumab causes these adverse effects. OBJECTIVE: assess whether the administration of this drug causes hypomagnesemia and secondary hypocalcemia, like other anti-EGFR. METHODS: patients on this study came from the controlled clinical assay: Use of Monoclonal Antibody Nimotuzumab in Treatment of Patients with Squamous-Cell Carcinoma of the Head and Neck In Advance Stages. 12 patients were taken by simple random sampling from each group of treatment of clinical assay (total 24). Demographic and anthropometric variables were recorded and mensuration of calcium and magnesium were done from serum samples obtained during clinical assay and preserved at 86 °C. Information was processed using statistical package SPSS 15.0. Friedman test and Wilcoxon test were used to assess changes in Ca and Mg concentrations. Wilcoxon-Mann-Whitney test was used to compare the groups. RESULTS: both groups of subjects had similar characteristics. In the group of patients treated with nimotuzumab, Magnesium concentrations mean were 2.06, 2.17 and 2.11 mg/dL, at the beginning, after three weeks and at the end of treatment, respectively (p=0.72). There were not differences in Mg and Ca concentration changes along the study between groups (p= 0.07 y p= 0.86). CONCLUSIONS: there are not evidences to establish that nimotuzumab causes hypomagnesaemia and secondary hypocalcaemia in treatment of 200 mg a week during six weeks.
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Humanos , Magnesio , Oncología Médica/métodos , Anticuerpos Monoclonales/uso terapéutico , BiomarcadoresRESUMEN
Introducción: las complicaciones neurológicas en la cirugía de los gliomas de alto grado están relacionadas con problemas en localización y exposición, extensión de la resección y la manera en que se manipulan los tejidos. Hay factores secundarios que contribuyen a la evolución desfavorable y la muerte precoz de un paciente.Objetivos: establecer la relación que existe entre la mortalidad en los primeros 30 días y diferentes factores de riesgo e identificar causas de muerte.Métodos: fueron operados 131 pacientes en el Servicio de Neurocirugía del Hospital Calixto García desde enero de 2005 a enero de 2010, con el diagnóstico de gliomas de alto grado. De ellos, 14 fallecieron en los primeros 30 días. Variables principales utilizadas: edad, localización tumoral, grado de resección quirúrgica y causas de la muerte. Se aplicó la prueba chi cuadrado de independencia con un nivel de significación de 0,05 para evaluar relación entre variables.Resultados: la mortalidad perioperatoria fue del 10,7 por ciento. El riesgo fue mayor en el sexo masculino; discretamente mayor en los mayores de 60 años. No estuvo relacionado con la localización del tumor. Operar con signos de enclavamiento cerebral, incrementó al máximo la probabilidad de fallecer en el primer mes. La resección parcial en relación con la total y con la biopsia mostró mayor probabilidad de mortalidad. No hubo muerte transoperatoria.Conclusiones: los factores que influyeron principalmente en la evolución desfavorable fueron: la baja puntuación en la escala de Karnofskyy una resección limitada, igual o menor que 50 por ciento en una craneotomía(AU)
Introduction: The neurological complications found in the high gradegliomas surgery are primarily related with location, exposure and extension of the resection and with the way of handling tissues. There are secondary factors that contribute to the unfavorable progression and even the early death of patients that suffers this disease.Objectives: To set the relationship between mortality within the first 30 days after surgery and the different risk factors, and to identify the causes of death.Methods: One hundred and thirty one patients diagnosed with high gradegliomas were operated on in the neurosurgery service of Calixto García hospital from January 2005 through January 2010. Fourteen of them died within the first thirty days. The study variables were age, tumor location, degree of surgical resection and causes of death. Chi-square test of independence with significance level of 0.05 was applied to evaluate the association among the variables.Results: The perioperative mortality rate was 10.7 percent. The risk of death was higher in males; slightly higher in those over 60 years and unrelated to the tumor location. If patients are operated on with signs of brain herniation, they are more likely to die in the first month. Partial compared to total resection and to biopsy showed higher mortality probabilities. There was no intraoperative death.Conclusions: The low scoring in the Karnofsky Scale, and a partial resection equal or smaller than 50 percent in a craniotomy were the influential factors in an unfavorable outcome of disease(AU)
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Humanos , Masculino , Femenino , Neoplasias Cerebelosas/cirugía , Neoplasias Cerebelosas/mortalidad , Neoplasias Cerebelosas/epidemiología , Epidemiología Descriptiva , Estudios Prospectivos , Estudios LongitudinalesRESUMEN
Introducción: las complicaciones neurológicas en la cirugía de los gliomas de alto grado están relacionadas con problemas en localización y exposición, extensión de la resección y la manera en que se manipulan los tejidos. Hay factores secundarios que contribuyen a la evolución desfavorable y la muerte precoz de un paciente. Objetivos: establecer la relación que existe entre la mortalidad en los primeros 30 días y diferentes factores de riesgo e identificar causas de muerte. Métodos: fueron operados 131 pacientes en el Servicio de nNeurocirugía del Hospital Calixto García desde enero de 2005 a enero de 2010, con el diagnóstico de gliomas de alto grado. De ellos, 14 fallecieron en los primeros 30 días. Variables principales utilizadas: edad, localización tumoral, grado de resección quirúrgica y causas de la muerte. Se aplicó la prueba chi cuadrado de independencia con un nivel de significación de 0,05 para evaluar relación entre variables. Resultados: la mortalidad perioperatoria fue del 10,7 por ciento. El riesgo fue mayor en el sexo masculino; discretamente mayor en los mayores de 60 años. No estuvo relacionado con la localización del tumor. Operar con signos de enclavamiento cerebral, incrementó al máximo la probabilidad de fallecer en el primer mes. La resección parcial en relación con la total y con la biopsia mostró mayor probabilidad de mortalidad. No hubo muerte transoperatoria. Conclusiones: los factores que influyeron principalmente en la evolución desfavorable fueron: la baja puntuación en la escala de Karnofskyy una resección limitada, igual o menor que 50 por ciento en una craneotomía(AU)
Introduction: The neurological complications found in the high gradegliomas surgery are primarily related with location, exposure and extension of the resection and with the way of handling tissues. There are secondary factors that contribute to the unfavorable progression and even the early death of patients that suffers this disease. Objectives: To set the relationship between mortality within the first 30 days after surgery and the different risk factors, and to identify the causes of death. Methods: One hundred and thirty one patients diagnosed with high gradegliomas were operated on in the neurosurgery service of Calixto García hospital from January 2005 through January 2010. Fourteen of them died within the first thirty days. The study variables were age, tumor location, degree of surgical resection and causes of death. Chi-square test of independence with significance level of 0.05 was applied to evaluate the association among the variables. Results: The perioperative mortality rate was 10.7 percent. The risk of death was higher in males; slightly higher in those over 60 years and unrelated to the tumor location. If patients are operated on with signs of brain herniation, they are more likely to die in the first month. Partial compared to total resection and to biopsy showed higher mortality probabilities. There was no intraoperative death. Conclusions: The low scoring in the Karnofsky Scale, and a partial resection equal or smaller than 50 percent in a craniotomy were the influential factors in an unfavorable outcome of disease(AU)
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Humanos , Masculino , Femenino , Causas de Muerte , Neoplasias Cerebelosas/mortalidad , Neoplasias Cerebelosas/cirugía , Glioma/cirugía , Factores de Riesgo , Epidemiología Descriptiva , Estudios Longitudinales , Estudios ProspectivosRESUMEN
Primary brain tumors constitute the most frequent solid tumor of childhood. High expression of the epidermal growth factor receptor (EGFR) protein has been associated with tumor progression and enhanced tumorigenicity in adult and children gliomas. Nimotuzumab is a humanized antibody that targets the EGFR and has proven efficacy in adult and children gliomas. To provide a new therapeutic option for patients with active, poor prognosis central nervous system (CNS) tumors and to evaluate the feasibility and safety of long-term nimotuzumab therapy in children with diverse CNS tumors, an expanded access program was launched at the Juan Manuel Marquez hospital. Patients were required to be 18 or younger and have one CNS tumor: low-grade glioma (LGG) or high-grade glioma (HGG), brainstem glioma (BSG), ependymoma or primitive neuroectodermal tumor (PNET), and a Lansky or Karnofsky performance status ≥40. Treatment consisted of weekly nimotuzumab administered at 150 mg/m(2) for 12 weeks, continuing every 14 days in the absence of severe condition worsening or unacceptable toxicity. Nimotuzumab was administered alone or in combination with radiotherapy, chemotherapy, or both, depending on the tumor type, stage, and previous treatment. Eighty-eight patients, 39 with BSG, 25 with HGG, 9 with progressive LGG, 9 with anaplastic ependymomas, and 6 with other tumor types, including PNET, neuroblastoma, meduloblastoma, and thalamic tumors, were treated with the antibody. The mean number of nimotuzumab doses was 36, from 1 to 108. The most frequent adverse events were mild to moderate skin rash, mucositis, vomiting, seizures, hypothermia, hyperthermia, and paleness. One patient had a grade 3 mucositis, while the other had a grade 3 bleeding on surgery. Sixteen children stopped treatment after at least 2 years with stable disease, partial or complete response. All children were able to maintain the best response achieved on treatment after a 3-year interruption. In summary, this study shows the feasibility of very prolonged administration of nimotuzumab together with the lack of rebound effect after treatment cessation.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Adolescente , Niño , Preescolar , Esquema de Medicación , Estudios de Factibilidad , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: The progressive decline in the immune function during ageing is termed immunosenescence. Previous studies have reported differences between males and females in the distribution and cell responses of lymphocyte subsets. Most studies of immunosenescence have been done in populations of industrialized countries living in a rather cold environment, and facing lower antigenic challenges such as Cytomegalovirus (CMV). The aim of this study was to determine the effect of ageing on lymphocytes in a population with a high prevalence of CMV infection in all ages, and to compare gender differences related to the immunosenescence markers. RESULTS: Different populations of peripheral blood leukocytes from healthy young and old IgG-CMV seropositive individuals were examined using flow cytometry. With age, the number and frequency of B cells and T cells significantly decreased, while highly differentiated T cells increased. Such changes were different in males and females. The age-associated decline of less differentiated lymphocyte subsets (CD19, CD4 and CD8 cells) and the increase of highly differentiated T cells were more prominent in females. In males, there were no significant changes in CD19, CD4 and CD8 subsets but there was a significant increase in the proportion of highly differentiated T cells. CONCLUSION: Shifts in lymphocyte subsets distribution were influenced by age and gender in an IgG-CMV seropositive population. These results suggest different patterns of immunosenescence in respect to gender differences. These patterns could have implications in the design of immunotherapy in the elderly.
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La investigación clínica no termina con el registro del nuevo medicamento, sino con la modificación de los indicadores de salud poblacional. Este artículo ilustra la experiencia de la biotecnología cubana en el propósito de contribuir a la reducción de la mortalidad por tumores malignos. En el control del cáncer, la biotecnología tiene cuatro espacios de impacto: el primero es en la prevención primaria mediante vacunas profilácticas, el segundo, consiste en las técnicas de diagnóstico precoz, el tercero es la estratificación de los pacientes mediante marcadores moleculares pronósticos o predictivos y el cuarto rol radica en el tratamiento de la enfermedad diseminada con vacunas terapéuticas y anticuerpos monoclonales que reconocen blancos específicos en los tumores. El uso de estas terapias ha traído consigo un cambio de paradigma del tratamiento del cáncer. La experiencia cubana ha sido exitosa debido a la existencia de un sistema de salud con altos estándares basado en la cobertura completa y equidad de acceso, el desarrollo del nivel primario de atención médica, centro de gravedad del sistema cubano y el desarrollo en las últimas tres décadas de una industria biotecnológica nacional, innovadora y con capacidad productiva para cubrir las necesidades nacionales de productos y exportar. A pesar de los avances, quedan grandes retos técnicos y metodológicos. La investigación científica posregistro permitirá trazar la estrategia para optimizar el impacto de los nuevos productos en la salud poblacional, encaminada a incrementar la esperanza de vida de los cubanos(AU)
The clinical research does not finish with the registration of a new drug, but with the modification of the population health indexes. This paper set forth the experience of the Cuban biotechnology in cancer control, in order to achieve the reduction of mortality rate from malignant tumors. Biotechnology has four areas of remarkable impact in cancer control: first, the primary prevention by means of prophylactic vaccines; second, the techniques for early diagnosis; third, the stratification of patients according to the molecular prognostic or predictive biomarkers and fourth, the treatment of advanced disseminated cancer with therapeutic cancer vaccines and monoclonal antibodies that detect specific targets in tumors. The use of these therapies has entailed a shift of paradigm in the cancer therapy. The Cuban experience has been successful due to the existence of a high standard health system based on complete coverage and equal access, the development of the primary medical care- the core of the Cuban health system -and the advance of a national, innovative biotech industry with manufacturing capacity to meet the national demand and to export products. In spite of the advances, big technical and methodological challenges still remain. Post-registration scientific research would define the strategy to optimize the impact of the new products in the population's health, aimed at increasing the life expectancy of the Cuban people(AU)
Asunto(s)
Biotecnología , Neoplasias/terapia , Vacunas contra el Cáncer , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
La investigación clínica no termina con el registro del nuevo medicamento, sino con la modificación de los indicadores de salud poblacional. Este artículo ilustra la experiencia de la biotecnología cubana en el propósito de contribuir a la reducción de la mortalidad por tumores malignos. En el control del cáncer, la biotecnología tiene cuatro espacios de impacto: el primero es en la prevención primaria mediante vacunas profilácticas, el segundo, consiste en las técnicas de diagnóstico precoz, el tercero es la estratificación de los pacientes mediante marcadores moleculares pronósticos o predictivos y el cuarto rol radica en el tratamiento de la enfermedad diseminada con vacunas terapéuticas y anticuerpos monoclonales que reconocen blancos específicos en los tumores. El uso de estas terapias ha traído consigo un cambio de paradigma del tratamiento del cáncer. La experiencia cubana ha sido exitosa debido a la existencia de un sistema de salud con altos estándares basado en la cobertura completa y equidad de acceso, el desarrollo del nivel primario de atención médica, centro de gravedad del sistema cubano y el desarrollo en las últimas tres décadas de una industria biotecnológica nacional, innovadora y con capacidad productiva para cubrir las necesidades nacionales de productos y exportar. A pesar de los avances, quedan grandes retos técnicos y metodológicos. La investigación científica posregistro permitirá trazar la estrategia para optimizar el impacto de los nuevos productos en la salud poblacional, encaminada a incrementar la esperanza de vida de los cubanos
The clinical research does not finish with the registration of a new drug, but with the modification of the population health indexes. This paper set forth the experience of the Cuban biotechnology in cancer control, in order to achieve the reduction of mortality rate from malignant tumors. Biotechnology has four areas of remarkable impact in cancer control: first, the primary prevention by means of prophylactic vaccines; second, the techniques for early diagnosis; third, the stratification of patients according to the molecular prognostic or predictive biomarkers and fourth, the treatment of advanced disseminated cancer with therapeutic cancer vaccines and monoclonal antibodies that detect specific targets in tumors. The use of these therapies has entailed a shift of paradigm in the cancer therapy. The Cuban experience has been successful due to the existence of a high standard health system based on complete coverage and equal access, the development of the primary medical care- the core of the Cuban health system -and the advance of a national, innovative biotech industry with manufacturing capacity to meet the national demand and to export products. In spite of the advances, big technical and methodological challenges still remain. Post-registration scientific research would define the strategy to optimize the impact of the new products in the population's health, aimed at increasing the life expectancy of the Cuban people
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Biotecnología , Vacunas contra el Cáncer , Neoplasias/terapiaRESUMEN
Se realizó un estudio analítico de casos-controles para evaluar la agregación familiar del cáncer en familiares de individuos con cáncer del pulmón. Los casos fueron 60 pacientes diagnosticados con cáncer de pulmón de células no pequeñas en estadios IIIB o IV, de la provincia Ciudad de La Habana; los controles fueron los cónyuges de los mismos. El mayor porcentaje de los casos es de sexo masculino, con un nivel de escolaridad secundario, no están expuestos a tóxicos, consumen vegetales menos de una vez por semana y fumaban antes del diagnóstico de la enfermedad. Además tienen antecedentes familiares de cáncer, y el diagnóstico de su enfermedad fue pasado los 55 años de edad con una evolución de entre uno y tres años. Dentro de los factores de riesgo para el cáncer del pulmón se encontraron el tabaquismo, el consumo insuficiente de vegetales en la dieta, la obesidad y el sedentarismo. Para el estudio de agregación familiar se calculó el Riesgo Relativo y el Odds Ratio que permitieron medir el grado de asociación tanto en las familias afectadas como en las no afectadas. Se encontró evidencia estadística de la existencia de agregación familiar para cáncer de cualquier localización anatómica(AU)
An analytical study of control cases was carried out to evaluate cancer family grouping in relatives of individuals with lung cancer. Sixty patients diagnosed with lung cancer of non-small cells in stages IIIB or IV, from the Havana City province were evaluated, the controls being their respective spouses. The larger per cent of cases were of masculine sex, with a secondary education level, non-exposed to toxic substances, eating vegetables at least once a week and were smokers before the diagnosis. They have previous family cases of cancer and they were diagnosed being 55 years old, with a subsequent evolution of 1 to 3 years. In The risk factors for lung cancer found were nicotine poisoning, insufficient eating of vegetables, obesity and sedentary life. Relative risk and odds ratio were computed for the family grouping study that allowed evaluating the association degree in the influenced families as well as in the uninfluenced ones. Significant influence of family grouping for cancer in any anatomical location was found(AU)
Asunto(s)
Humanos , Neoplasias Pulmonares/patología , Estudios de Casos y ControlesRESUMEN
PURPOSE: We show the result of a randomized phase II clinical trial with an epidermal growth factor (EGF)-based cancer vaccine in advanced non-small-cell lung cancer (NSCLC) patients, evaluating immunogenicity, safety, and effect on survival. PATIENTS AND METHODS: Eighty patients with stage IIIB/IV NSCLC after finishing first-line chemotherapy were randomly assigned to receive best supportive care or EGF vaccinations. RESULTS: Vaccination was safe. Adverse events were observed in less than 25% of cases and were grade 1 or 2 according to National Cancer Institute Common Toxicity Criteria. Good anti-EGF antibody response (GAR) was obtained in 51.3% of vaccinated patients and in none of the control group. Serum EGF concentration showed a major decrease in 64.3% of vaccinated patients. GAR patients survived significantly more than those with poor antibody response (PAR). Also, patients whose serum EGF dropped below 168 pg/mL survived significantly more than the rest. There was a trend to an increased survival for vaccinated patients compared with controls. The survival advantage for vaccinated patients compared with controls was statistically significant in the subgroup of patients with age younger than 60 years. CONCLUSION: Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.