Is there a subgroup of long-term evolution among patients with advanced lung cancer?: Hints from the analysis of survival curves from cancer registry data

Background: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. Methods: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short-and long-term survivors. Bayesian information criterion was used for model selection. Results: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. Conclusions: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short-and long-term survival subpopulations should be considered in clinical research.LS, PL, CV, TC, AL were funded by their employer the Center of Molecular Immunology. YG is funded by the Ministry of Health. JB received no funding. We thank Dr. Camilo Rodriguez for their contribution to this work and for facilitate literature needed for manuscript writing

Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients

The prognosis of patients with advanced non small cell lung (NSCLC) cancer remains dismal. Epidermal Growth Factor Receptor is over-expressed in many epithelial derived tumors and its role in the development and progression of NSCLC is widely documented. CimaVax-EGF is a therapeutic cancer vaccine composed by human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. CimaVax-EGF has been evaluated so far in more than 1000 advanced NSCLC patients, as second line therapy. Two separate studies were compared to assess the impact of high dose vaccination at multiple anatomic sites in terms of immunogenicity, safety and preliminary efficacy in stage IIIb/IV NSCLC patients. In both clinical trials, patients started vaccination 1 month after finishing first line chemotherapy. Vaccination at 4 sites with 2.4 mg of EGF (high dose) was very safe. The most frequent adverse events were grade 1 or 2 injection site reactions, fever, headache and vomiting. Patients had a trend toward higher antibody response. The percent of very good responders significantly augmented and there was a faster decrease of circulating EGF. All vaccinated patients and those classified as good responders immunized with high dose at 4 sites, had a large tendency to improved survival

Equivalencia terapéutica entre IOR® EPOCIM y EPO sin albúmina en pacientes con insuficiencia renal crónica en hemodiálisis

Ensayo Clínico Fase II-III, controlado, monocéntrico, a doble ciegas y aleatorizado, para evaluar la eficacia y seguridad del tratamiento con EPO Sin/Albúmina con un nuevo estabilizante y determinar la equivalencia terapéutica de esta formulación con el ior® EPOCIM, en enfermos hemodializados. Se incluyeron 60 pacientes, en hemodiálisis iterada 3 veces por semana, Kt/V mayor 1.2, los que mantuvieran niveles iguales o superiores de 10 g/l  de Hemoglobina  durante al menos 3 meses, tratados con ior® EPOCIM, divididos en 2 grupos, con 30 pacientes cada uno. El primero, recibió con EPO S/A la dosis habitual de Eritropoyetina y el segundo, con ior® EPOCIM, ambos por vía subcutánea en dosis 1:1 sin modificación de la dosis, evaluando la respuesta hematológica  (hemoglobina/ hematocrito) de ambos productos. Los grupos de tratamiento fueron homogéneos, según las variables analizadas: la edad media para el grupo EPO SA fue de 43.8 años, mientras para el grupo ior® EPOCIM  fue de 46.8 años;  la media del peso seco fue de 61.1 Kg vs. 60.4 Kg. La dosis de Eritropoyetina administrada solo fue variada en dependencia del cambio de peso del enfermo entre la dosis al inicio y al final de las 12 semanas: EPO S/A 7482.9 vs. 7485.4 UI/Kg/semanal y ior® EPOCIM 8045.3  vs. 8018.6 UI/Kg/semanal. Los resultados iniciales del hematocrito (35.9% vs. 36.6%) y de la hemoglobina (11.6 vs. 11.7 g/dl) mostraron que las medias del hematocrito, para ambos grupos, al final del estudio, tuvieron una diferencia inferior a 3 %  (33.8 vs. 34.5) y en la hemoglobina inferior a 1 g/dl (10.6 vs.  10.7),  con una disminución ligera al final del tratamiento similar para ambos grupos. Los eventos adversos detectados fueron: dolor en el sitio de la inyección (63 %), hipotensión (53.3 %), calambre (31.7 %) y cefaleas (15 %) atribuibles al proceder de hemodiálisis, con un perfil de seguridad propio de enfermos en hemodiálisis. No se observaron diferencias estadísticas significa-tivas entre los grupos (p=0.5938). Los resultados permiten sugerir la equiva-lencia terapéutica entre EPO S/A y EPOCIM. Se requiere la extensión en tiempo del fármaco; vigilancia de este nuevo producto para establecer sus efectos a largo plazo.  Palabras clave: anemia, eritropoyetina, hemodiálisis, insuficiencia renal crónica, ensayo clínico

Metodología y sistemas para meta-análisis de ensayos clínicos

Introducción: Frecuentemente la información médica sobre determinado aspecto clínico, es tan poco clara y contradictoria, que en ocasiones el profesional de la salud no tiene el tiempo o la orientación para poder analizarla en su totalidad, y poder así aprovecharla en su real magnitud.Objetivo: Revisar la metodología y los sistemas que existen para realizar meta-análisis de ensayos clínicos.Métodos: Se ha revisado el proceso de análisis de esos conocimientos, llamado meta-análisis; éste es un estudio sistemático, cualitativo y cuantitativo de un grupo de informes o artículos de investigación, generalmente enfocado al análisis de un aspecto clínico.Resultados: En este artículo de revisión, se muestra cómo se diseña, ejecuta y reporta el meta-análisis, así como los pasos para su realización.Discusión: Se resumen y se comparan los sistemas que más se utilizan para realizar meta-análisis.Conclusiones: Con este trabajo se conoce que los análisis de sensibilidad, acumulado y de sesgo de publicación no pueden faltar para un meta-análisis, así como los sistemas donde poder realizar cada uno de estos análisis.Palabras clave: metodología; ensayos clínicos; meta-análisis.</p

Pharmacokinetics evaluation of nimotuzumab in combination with doxorubicin and cyclophosphamide in patients with advanced breast cancer

EGFr (Epidermal growth factor receptor) overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb (monoclonal antibody) that recognizes an epitope located in the extracellular domain of human EGFr. The aim of this study was to assess the pharmacokinetics of nimotuzumab in patients with locally advanced breast cancer who are receiving neoadyuvant therapy combined with the AC chemotherapy regimen (i.e., 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide in 4 cycles every 21 days). A single center, non-controlled, open Phase I clinical trial, with histopathological diagnosis of locally advanced stage III breast cancer, was conducted in 12 female patients. Three patients were enrolled at each of the following fixed dose levels: 50, 100, 200 and 400 mg/week. Multiple intermittent short-term intravenous infusions of nimotuzumab were administered weekly, except on weeks 1 and 10, when blood samples were drawn for pharmacokinetic assessments. Nimotuzumab showed dose-dependent kinetics. No anti-idiotypic response against nimotuzumab was detected in blood samples of participants. There was not interaction between the administration of nimotuzumab and chemotherapy at the dose levels studied. The optimal biological doses ranging were estimated to be 200 mg/weekly to 400 mg/weekly

Quality of Life related to health in the morbidity of periodic hemodialysis patient

Foundation: chronic renal failure has a negative impact in the quality of life and constitutes a morbidity predictor in patients with periodic hemodialysis.Objective: to evaluate the influence of quality of life related to health in the morbidity of patients in intermittent periodic hemodialysis.Methods: a descriptive study was done in patients with three or more time of intermittent periodic hemodialysis at the Nephrology service of the Military Hospital Dr. Carlos J. Finlay. Havana, in a 12 month follow up period. The variables analyzed were: age, sex, time with the substituting renal function treatment, morbidity rate, type of morbidity in hemodialysis and hospital admission rate. A questionnaire for quality of life in patients with renal disease (version 1.3) was applied.Results: patients under 60 years old predominated, of high schooling level, with blood hypertension mainly due to renal failure.  The most frequent morbidities were: chills, arterial Hypotension, and complications related to vascular access. The admission rate was low. The summary physical component had the lower punctuation followed by the summary mental component. Among these and age there was found an inversely proportional correlation, so as the morbidity rate and the summary physical component.Conclusion: the results obtained are related to preceding studies. The physical component summary results with higher involvement, mainly in the older adult, considering the negative relation with the morbidity rate and hospital admission.</p

Characterization of participants adolescents in the clinical trial with Abdala vaccine

Introduction: The clinical evaluation of anti-COVID-19 vaccines in pediatric population, is a challenge in times of pandemic, to respond to the urgency of representative samples that contribute to the reproducibility of the study in the real population. Objective: To characterize the adolescents participating in the clinical trial with the Abdala anti-COVID-19 vaccine, to evaluate compliance with the vaccination schedule and to estimate whether they are representative of this population group. Methods: Data from a phase II trial with Abdala vaccine were used. A total of 703 subjects were included, 207 (29.4 %) of them were adolescents, between 12 and 18 years of age, with apparently healthy or controlled chronic diseases, nutritional assessment between 10 and 90 percentiles, and willingness to participate in the study. Sociodemographic data, personal pathological history, toxic habits and compliance with the vaccination scheme of 3 doses every 14 days were the variables studied. Results: The average age was 15 years, it was predominant female sex (51.7 %), white skin color (55.6 %) and nutritional assessment above 75 to 90 percentiles (40.6 %). The 9.6 % had toxic habits such as smoking and ingestion of alcoholic beverages. Some personal pathological history was in 51.2 % with a higher prevalence for bronchial asthma, rhinitis and other allergies. The vaccination scheme was fulfilled for 95.8 % of individuals. Conclusions: Sociodemographic characteristics, pathological history and toxic habits described for adolescents on the study are representative for this population group in Cuba. The vaccination schedule had an optimal compliance

Efficacy of nimotuzumab according to inflammatory indices in patients with advanced non-small cell lung cancer

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

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] 15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activityS

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics

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 registrationhttps://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205