RESUMO
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)
Assuntos
Humanos , Adolescente , Prognóstico , Resultado do Tratamento , Carcinoma Pulmonar de Células não Pequenas/ultraestrutura , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Estudos Longitudinais , Estudo de AvaliaçãoRESUMO
RESUMEN El cáncer es un problema prioritario de salud pública en el mundo. En Cuba constituye la segunda causa de muerte en la mayoría de grupos de edades y fundamentalmente en la población mayor de 60 años. El objetivo fue evaluar el impacto de la inmunoterapia como una alternativa terapéutica que mejora las funciones de supervivencia en pacientes ancianos con cáncer de pulmón de células no pequeñas. Se realizó un estudio analítico experimental donde el universo estuvo integrado por 123 ancianos con diagnóstico de cáncer de pulmón los cuales fueron tratados con inmunoterapia en Matanzas. Fueron utilizadas variables de control a las cuales se les aplicaron las medidas de resumen correspondientes utilizando las pruebas de hipótesis de chi cuadrado y las razones de verosimilitud para su análisis y estadístico y fueron evaluadas las funciones de supervivencia usando las curvas de Kaplan Meier. Se demostró la eficacia y seguridad de la inmunoterapia en el tratamiento de los pacientes estudiados. Por ello consideramos que el impacto secuencial de la combinación de la cirugía, la quimioterapia, la radioterapia y las terapias biológicas, tiende a prolongar la supervivencia de los pacientes que sufren cáncer de pulmón de células no pequeñas con una calidad de vida éticamente aceptable. Las nuevas terapias inmunológicas que consisten en devolver al sistema inmunológico de los pacientes, la capacidad de reconocer al tumor como extraño, y por tanto luchar contra él; han producido respuestas y beneficios muy importantes (AU).
SUMMARY Cancer is a priority public health problem in the world. In Cuba, it is the second cause of death in most age groups and mainly in the population aged over 60 years. To evaluate the impact of immunotherapy as a therapeutic alternative that improves survival functions in elder patients with non-small cell lung cancer. An experimental analytical study was carried out; the universe was composed by 123 elder people diagnosed with lung cancer who were treated with immunotherapy in Matanzas. Control variables were used to which the corresponding summary measures were applied using chi-square hypothesis tests and likelihood ratios for their analysis and statistics; survival functions were evaluated using Kaplan Meier curves. The efficacy and safety of immunotherapy in the treatment of the studied patients was demonstrated. Therefore, the authors believe that the sequential impact of the combination of surgery, chemotherapy, radiotherapy and biological therapies tends to extend the survival of patients suffering from non-small cell lung cancer with an ethically acceptable life quality. The new immunological therapy, consisting in returning to the patients´ immunologic system the capacity of recognizing a tumor as foreign, and therefore, fighting against it, have yielded very important answers and benefits (AU).
Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Ensaio Clínico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Epidemiologia Analítica , SobrevivênciaRESUMO
BACKGROUND: CIGB-247, a VSSP-adjuvanted VEGF-based vaccine, was evaluated in a phase I clinical trial in patients with advanced solid tumors (CENTAURO). Vaccination with the maximum dose of antigen showed an excellent safety profile, exhibited the highest immunogenicity and was the only one showing a reduction on platelet VEGF bioavailability. However, this antigen dose level did not achieve a complete seroconversion rate in vaccinated patients. These clinical results led us to the question whether a "reserve" of untapped immune response potential against VEGF could exist in cancer patients. To address this matter, CENTAURO-2 clinical trial was conducted where antigen and VSSP dose scale up were studied, and also incorporated the exploration of aluminum phosphate as adjuvant. These changes were made with the aim to increase immune response against VEGF. RESULTS: The present study reports the characterization of the humoral response elicited by CIGB-247 from the combining of different antigen doses and adjuvants. Cancer patients were immunologically monitored for approximately 1 year. Vaccination with different CIGB-247 formulations exhibited a very positive safety profile. Cancer patients developed IgM, IgG or IgA antibodies specific to VEGF. Elicited polyclonal antibodies had the ability to block the interaction between VEGF and its receptors, VEGFR1 and VEGFR2. The highest humoral response was detected in patients immunized with 800 µg of antigen + 200 µg of VSSP. Off-protocol long-term vaccination did not produce negative changes in humoral response. CONCLUSIONS: Vaccination with a human VEGF variant molecule as antigen in combination with VSSP or aluminum phosphate is immunogenic. The results of this study could contribute to the investigation of this vaccine therapy in an adequately powered efficacy trial. TRIAL REGISTRATION: Trial registration number: RPCEC00000155. Cuban Public Clinical Trial Registry. Date of registration: June 06, 2013. Available from: http://registroclinico.sld.cu/ .
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Anticâncer/imunologia , Imunidade Humoral/imunologia , Imunoterapia Ativa , Neoplasias/imunologia , Neoplasias/terapia , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/administração & dosagem , Chlorocebus aethiops , Feminino , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/sangue , Coelhos , Receptores de Fatores de Crescimento do Endotélio Vascular/sangue , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Se presentó una paciente de 35 años de edad con un infrecuente leiomiosarcoma pleomórfico de vejiga de alto grado de malignidad, con una historia de hematuria total de 7 meses de evolución. El diagnóstico de tumor vesical se realizó por cistoscopia, urograma descendente y tomografía axial computarizada. El tipo histológico del tumor, leiomiosarcoma pleomórfico, se realizó por tinciones especiales de IHQ-Alfa-Actina, específica para este tipo de tumor. El tratamiento quirúrgico fue cistectomía parcial seguida de quimioterapia coadyuvante. Se describieron los resultados, y evolución de la paciente hasta los 5 años. Actualmente la paciente se encuentra libre de tumor, y mantiene una vida sin problemas. Se revisó la literatura al respecto.
We presented a female patient, aged 35 years old, with an infrequent bladder pleomorphic leiomyosarcoma of malignancy high level. She had a history of total hematuria of 7 months of evolution. We arrived to the diagnosis of the vesical tumor by citoscopy, descendent urogram and computerized axial tomography. The histological type of the tumor, a pleomorphic leiomyosarcoma, was determined by special IHQ-Alpha-Actin, specific for this kind of tumor. The surgical treatment by cystectomy was partial, followed of coadjutant chemotherapy. We described the results and the patients' evolution during 5 years. Currently the patient is tumor free, and lives her life without problems. We reviewed the literature on the theme.