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

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC.

Background: CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC. Methods: Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design. Toxicities were graded according to CTCAE V4.03. Thirteen patients (one unevaluable), the majority with PD-L1 0%, were enrolled into two dose levels of CIMAvax-EGF. Findings: The combination was determined to be safe and tolerable. The recommended phase 2 dose of CIMAvax-EGF was 2.4 mg. Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

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.

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer.

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.

Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study.

BACKGROUND: Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. METHODS: A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. RESULTS: Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.

Tratamiento psicofarmacológico del trastorno bipolar: Una revisión necesaria / Pharmacological treatment of bipolar disorder: A necessary revision

El trastorno bipolar (TB) es uno de los trastornos psiquiátricos de mayor importancia en la actualidad. El tratamiento psicofarmacológico es un elemento importante en el manejo de estos pacientes. En el presente trabajo nos proponemos revisar las tendencias actuales en el tratamiento psicofarmacológico del trastorno bipolar. Para la realización de este trabajo nos basamos en los resultados de una búsqueda bibliográfica de las principales bases de datos sobre el tema. Podemos concluir en que el tratamiento psicofarmacológico del trastorno bipolar se caracteriza por la gran variedad de grupos farmacológicos utilizados, dentro de los cuales el litio continúa ocupando un lugar relevante(AU)

Introduction. Bipolar Disorder (BD) is one of the most important psychiatric disorders nowadays. Pharmacological treatment is an important element in the management of these patients. In this paper we aim to make a review about currents tendencies used in pharmacological treatment of B.D. Methods. A bibliographic searching of additional sources about this topic was the psychopharmacological treatment of bipolar includes the use of several psychotropic drugs, among which, lithium keeps a relevant position(AU)

Utilización de antipsicóticos en el Hospital Psiquiátrico de La Habana durante los años 2006 y 2007 / Use of antipsychotics at the Psychiatric Hospital of Havana during 2006-2007

Introducción: El descubrimiento de los antipsicóticos constituyó un paso importante en el tratamiento de los trastornos mentales. Debido a los efectos neurológicos adversos asociados a su uso inicialmente se les denominó neurolépticos. Posteriormente surgieron otros antipsicóticos (atípicos), con menor frecuencia de aparición de estos efectos pero con un mayor costo. El objetivo de nuestro trabajo es identificar cuál de los dos grupos es el más utilizado en el Hospital Psiquiátrico de La Habana. Métodos: Se realizó un estudio observacional y retrospectivo de todas las órdenes de salida de antipsicóticos de la farmacia hospitalaria durante el período estudiado. Resultados: El grupo de antipsicóticos más utilizado fue el de los clásicos (99,41 por ciento). En el último año estudiado se observó un discreto incremento en el uso de los atípicos con respecto al año anterior (0,84 por ciento vs. 0,37 por ciento). Conclusiones: Los antipsicóticos clásicos son el principal grupo de antipsicóticos utilizados en el Hospital Psiquiátrico de La Habana(AU)

Introduction: The discovery of antipsychotics was an important contribution to the treatment of mental disorders. They were previously named neuroleptics due to the neurological adverse reactions associated to their use. Afterwards, other (atypical) antipsychotics with less frequency of neurological adverse reactions appeared; but with a higher cost. The aim of this work is to identify which of the two groups is more used at the Psychiatric Hospital of Havana. Method and Material: An observational retrospective studied was developed about all antipsychotic orders from the drugstore to the wards of the hospital during 2006- 2007. Results: The classical group of antipsychotics was the most used (99.41 percent). A little increased in the use of atypical antipsychotic was observed in 2007 compared with the previous year(0.84 percent vs 0.37 percent). Conclussions: Classical antipsychotics are the main group of antipsychotics used in the Havana Psychiatric Hospital(AU)

Drogas recientemente desarrolladas en el tratamiento de la depresión unipolar / Recent drugs developed in unipolar depression

Objetivo: reportar los resultados obtenidos en la investigación de 2 nuevas drogas utilizadas en el tratamiento de la depresión unipolar. Desarrollo: los estudios realizados muestran que la duloxetina y la agomelatina son 2 fármacos eficaces para el tratamiento de la depresión unipolar. La duloxetina es un inhibidor de la recaptación de serotonina y noradrenalina. La agomelatina posee un novedoso mecanismo de acción que brinda un perfil de efectos adversos diferente al del resto de los antidepresivos. Conclusiones: la duloxetina no es un verdadero nuevo antidepresivo, sus propiedades son similares a las de la venlafaxina o el minalcipram, pero la agomelatina parece tener un perfil completamente diferente, agonista MT1 y MT2 y 5-HT2c. Sería de interés ver si la agomelatina expande el espectro del tratamiento de la depresión unipolar(AU)

Objective: To report the results obtained in the investigation of two new drugs used in the treatment for the unipolar depression.Development: Scientific studies show that Duloxetina and Agomelatina are effective on the treatment for the unipolar depression. Duloxetina is an inhibitor of Serotonin and Noradrenalins recaptation.Agomelatina has an original mechanism of action that provokes an adverse effect profile different from the rest of antidepressants.Conclusions: Duloxetina is not an authentic original antidepressant; its properties are similar to the ones of Venlafaxina (Efexor) or of Minalcipram, but Agomelatina seems to have a completely different profile, MT1, MT2 and 5HT2c agonist.It would be interesting to find out if Agomelatina wides the spectrum of unipolar depression treatment(AU)