The effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab for patients with inoperable esophageal squamous cell carcinoma / 中华放射医学与防护杂志

Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.

Nimotuzumab combinado con radioterapia en el tratamiento de tumores infiltrantes y difusos del tallo cerebral en niños y adolescentes

RESUMEN Introducción: Los gliomas infiltrantes y difusos del tallo cerebral en los niños y adolescentes comportan un mal pronóstico y un tiempo corto de supervivencia. Objetivo: Presentar los resultados obtenidos con la combinación de nimotuzumab y radioterapia en tumores del tallo cerebral en niños y adolescentes. Métodos: El anticuerpo monoclonal nimotuzumab combinado con la radioterapia fue aplicado en una serie de 69 pacientes con edades entre 2 y 18 años, incluidos desde 2008 hasta 2020, y seguidos hasta agosto de 2021. Fueron irradiados en el Instituto Nacional de Oncología y Radiobiología de La Habana, con una dosis en un rango de 54 a 59 Gy. El nimotuzumab se aplicó a la dosis de 150 mg/m2 de superficie corporal, una vez por semana mientras duró el tratamiento radiante, luego cada 2 semanas con igual dosis, y finalmente, una vez por mes durante 1, 2 o más años. Resultados: Al terminar el tratamiento combinado de la radioterapia y el nimotuzumab existió respuesta en 89,9 % de los pacientes. La mediana del tiempo de supervivencia global fue de 18,8 meses y las tasas de supervivencia de la serie fueron de 76,4; 45,4; 38,9; 32,8 y 31,5 % a uno, dos, tres, cuatro, cinco y más años, respectivamente, estabilizada a partir de este tiempo hasta diez años y más. Tres pacientes en recaída fueron reirradiados. Conclusiones: La combinación de radioterapia y nimotuzumab fue bien tolerada y es una opción de tratamiento en tumores del tallo cerebral en niños y adolescentes.

ABSTRACT Introduction: Infiltrating and diffuse gliomas of the brain stem in children and adolescents lead to a poor prognosis and a short survival time. Objective: Present the results obtained with the combination of nimotuzumab and radiotherapy in brain stem tumors in children and adolescents. Methods: The monoclonal antibody called nimotuzumab combined with radiotherapy was applied in a series of 69 patients aged between 2 and 18 years, from 2008 to 2020, and followed until August 2021. They were irradiated at the National Institute of Oncology and Radiobiology in Havana, with a dose in a range of 54 to 59 Gy. Nimotuzumab was applied at the dose of 150 mg/m2 of body surface area, once a week while the radiation treatment was active, then every 2 weeks with the same dose, and finally once a month for 1, 2 or more years. Results: At the end of the combined treatment of radiotherapy and nimotuzumab, there was a response in 89.9% of the patients. The median overall survival time was 18.8 months and series survival rates were 76.4; 45.4; 38.9; 32.8; and 31.5% at one, two, three, four, five and more years, respectively, and it was stabilized from this time to 10 years and more. Three relapsed patients were re-radiated. Conclusions: The combination of radiotherapy and nimotuzumab was well tolerated and is an option for the treatment in brain stem tumors in children and adolescents.

Eventos adversos del nimotuzumab en pacientes con tumor cerebral primario / Adverse events to the nimotuzumab in patients with primary cerebral tumor

Introducción: El nimotuzumab es un anticuerpo monoclonal empleado en el tratamiento de pacientes con tumor cerebral. Dada su novedad se justifica la realización de estudios de farmacovigilancia que avalen su seguridad. Objetivo: Caracterizar los eventos adversos relacionados con este medicamento en la práctica médica habitual. Métodos: Se realizó un estudio descriptivo y transversal de 41 pacientes con tumor cerebral primario tratados con nimotuzumab en el Departamento de Ensayos Clínicos del Hospital Provincial Docente Saturnino Lora Torres de Santiago de Cuba, desde mayo de 2017 hasta abril de 2019. Resultados: En la serie se identificaron 31 eventos adversos, de los cuales 17 eran conocidos y 14 desconocidos. Predominaron la cefalea (80,5 %), la debilidad en miembros inferiores (48,8 %) y la fosfatasa alcalina elevada (41,5 %). Cabe destacar que el total de los efectos no deseados se consideraron ligeros, según su intensidad; reversibles, según sus resultados y sin cambios, según la actitud respecto al medicamento. Conclusiones: Las características de los eventos adversos encontrados se asemejan a las descritas en otros estudios que también avalan la seguridad del fármaco.

Introduction: The nimotuzumab is a monoclonal antibody used in the treatment of patients with cerebral tumor. The realization of pharmaco surveillance studies that guaranteed its security is justified given its new features. Objective: To characterize the adverse events related to this medicine in the habitual medical practice. Methods: A descriptive and cross-sectional study of 41 patients with primary cerebral tumor treated with nimotuzumab in the Clinical Trial Department of Saturnino Lora Torres Teaching Provincial Hospital was carried out in Santiago de Cuba, from May, 2017 to April, 2019. Results: In the series 31 adverse events were identified, of which 17 were known and 14 were unknown. There was a prevalence of the headache (80.5 %), weakness in lower members (48.8 %) and the high alcaline phosphatase (41.5 %). It is necessary to highlight that all the non wanted effects were considered light according to the intensity; reversible, according to the results and without changes, according to the attitude regarding the medicine. Conclusions: The characteristics of the adverse events that were found resemble to those described in other studies that also guarantee the security of the drug.

Advances of nimotuzumab in the treatment of esophageal squamous cell carcinoma / 国际肿瘤学杂志

Esophageal squamous cell carcinoma (ESCC) is the most predominant pathological type of esophageal cancer in China. In recent years, with the development of molecular targeted drugs, targeted therapy has become a hot research topic in the field of ESCC treatment. Nimotuzumab is the first humanized monoclonal antibody targeting epidermal growth factor receptor (EGFR) in China, which has been approved for the treatment of early or locally advanced nasopharyngeal carcinoma. Several phase Ⅱ-Ⅲ clinical trials have explored the use of nimotuzumab in the treatment of ESCC, confirming its significant efficacy and survival benefit in the treatment of advanced ESCC, as well as its favorable safety profile.

Índice pronóstico nutricional en pacientes con cáncer de páncreas avanzado tratados con nimotuzumab combinado a quimioterapia / Nutritional prognostic index in patients with advanced pancreatic cancer treated with nimotuzumab combined with chemotherapy

Introducción: El índice pronóstico nutricional es un marcador inmuno-nutricional que puede ser útil como factor pronóstico en tumores gastrointestinales. Objetivo: Evaluar supervivencia de pacientes con adenocarcinoma pancreático avanzado tratados con quimioinmunoterapia según índice pronóstico nutricional, según parámetros clínico-patológicos y tratamiento. Métodos: Se realizó estudio retrospectivo y observacional en pacientes que recibieron quimioterapia gemcitabina-oxaliplatino combinado a nimotuzumab (n=118), en el Hospital Ameijeiras, entre 2014 y 2019. Se evaluó supervivencia por método Kaplan-Meier, y regresión de Cox, para determinar los factores pronósticos independientes de supervivencia. Resultados: El punto de corte seleccionado fue 40 (sensibilidad 52,9 por ciento y especificidad 85,7 por ciento (p = 0,019), con área bajo la curva de 0,693. Para pacientes con índice menor de 40, la supervivencia fue más baja respecto a los pacientes con índice ≥ 40 (11,4 meses frente a 16,0 meses; p=0,001), con un HR de 1,7 (1,13-2,60; p=0,011). Las variables mayormente asociadas con índice pronóstico nutricional altos son pacientes con sesenta años o menos; ECOG cero, índice de masa corporal ≥25 Kg/m2 y albúmina sérica >3,5g/dL (x² < 0,05). Los pacientes con índice ≥ 40 tienen medianas de supervivencia más altas que pacientes con índice < 40 en las variables seleccionadas con p < 0,05, excepto el índice de masa corporal. Conclusiones: Este trabajo constituye el primer reporte nacional de utilización del índice pronóstico nutricional como pronóstico de supervivencia en pacientes con cáncer de páncreas avanzado(AU)

Background: The nutritional prognostic index is an immuno-nutritional marker that can be useful as a prognostic factor in gastrointestinal tumors. Aim: To evaluate the survival of patients with advanced pancreatic adenocarcinoma treated with chemoimmunotherapy according to the nutritional prognostic index, according to clinical-pathological parameters and treatment. Methods: A retrospective and observational study was carried out in patients who received gemcitabine-oxaliplatin chemotherapy combined with nimotuzumab (n=118), at the Ameijeiras Hospital, between 2014 and 2019. Survival was evaluated by the Kaplan-Meier method, and Cox regression, for determine independent prognostic factors for survival. Results: The selected cut-off point was 40 (52.9 percent sensitivity and 85.7 percent specificity) (p=0,019), with an area under the curve of 0,693. For patients with an index less than 40, survival was lower compared to patients with index ≥ 40 (11, 4 months vs. 16, 0 months; p=0,001), with a HR of 1, 7 (1, 13-2, 60; p=0,011). The variables mostly associated with nutritional prognostic index patients with 60 years or less, ECOG 0, body mass index ≥ 25 kg/m2 and serum albumin >3,5g/dL (x2 < 0, 05). Patients with index ≥ 40 have higher median survival than patients with index < 40 in the selected variables with p < 0, 05, except body mass index. Conclusions: This work constitutes the first national report on the use of the nutritional prognostic index as a prognosis of survival in patients with advanced pancreatic cancer(AU)

Safety and efficacy of nimotuzumab combined with IMRT radiotherapy in the treatment of elderly patients with locally advanced cervical cancer / 中华放射医学与防护杂志

Objective:To investigate the safety and efficacy of nimotuzumab combined with IMRT radiotherapy in the treatment of elderly patients with locally advanced cervical cancer (LACC).Methods:A retrospective analysis was conducted for 34 elderly LACC patients treated with nimotuzumab combined with IMRT radiotherapy or concurrent chemoradiotherapy in the Zhangzhou Affiliated Hospital of Fujian Medical University from June 2020 to December 2021. The efficacy and side effects were evaluated one and two years after treatment.Results:Median follow-up time was 13.3 months (6.1-24.3 months). A total of 24 cases of complete response (CR) and eight cases of partial response (PR) were achieved after treatment, with an objective response rate (ORR) of 94.1% (32/34). The tumor diameters were (49.56 ± 19.22) mm before treatment and (19.61 ± 14.59) mm after treatment, with a tumor regression rate (TRR) of 59.22%.The 1- and 2- year progression-free survival (PFS) rates were 84.9% and 84.9%, overall survival (OS) rates 91.8% and 87.2%, respectively, disease-free survival (DFS) rates 91.8% and 87.2%, respectively, and the cancer-specific survival (CSS) rates 95.7% and 90.9%, respectively. The main adverse events included radiation enteritis, leukopenia, hypoproteinemia and anemia.Conclusions:Nimotuzumab combined with IMRT radiotherapy or concurrent chemoradiotherapy is safe and effective in the treatment of LACC.

Nimotuzumab combinado con un esquema de quimioterapia GEMOX en pacientes con cáncer pancreático avanzado / Nimotuzumab combined with GEMOX chemotherapy regimen in patients with advanced pancreatic cancer

Se realizó un estudio retrospectivo y observacional en pacientes con adenocarcinoma pancreático avanzado, tratados con Nimotuzumab combinado con un esquema de quimioterapia GEMOX, atendidos en el Servicio de Oncología Clínica del Hospital Clínico Quirúrgico Hermanos Ameijeiras entre 2013 y 2019 (n=118), cuyo objetivo fue evaluar la respuesta al tratamiento y la supervivencia global según variables clínicas, histopatológicas y tratamiento. Se utilizó método chi-cuadrado para la asociación de variables. Se evaluó la supervivencia global por el método de Kaplan Meier y se utilizó la prueba de Log-Rank y Breslow para la comparación de las curvas, con valor p<0.05. La tasa de control de la enfermedad fue 44,9. La mediana de supervivencia fue de 13,8 meses (IC95 por ciento:11,7-15,8). Las variables estadísticamente significativas asociadas con mayor respuesta al tratamiento y supervivencia fueron: no hábitos tabáquicos; índice plaquetas-linfocitos por debajo de 200; tumores primarios T2-T3, de localización predominantemente en cabeza pancreática; no presencia de metástasis al diagnóstico y más de seis dosis de quimioterapia o Nimotuzumab. Los pacientes con clasificación de bajo peso y albúmina sérica baja tuvieron peor supervivencia (p<0.05). En 42 pacientes se realizó una segunda línea de quimioterapia y se obtuvo supervivencia de 17,4 meses (IC95 por ciento:13,5-21,4). Las toxicidades clasificadas como grado 3-4 se reportaron en 27 pacientes (22,9 por ciento), las más frecuentemente observadas fueron: neuropatía (14,4 por ciento), neutropenia (10,2 por ciento) y trombopenia (9,3 por ciento). En condiciones de práctica clínica, con el Nimotuzumab combinado con quimioterapia GEMOX se obtuvieron óptimas tasas de control de la enfermedad y supervivencia con buen perfil de seguridad(AU)

A retrospective and observational study was carried out in patients with advanced pancreatic adenocarcinoma, treated with Nimotuzumab combined with a GEMOX chemotherapy scheme, in the Clinical Oncology Service at the Ameijeiras Hospital, between 2013 and 2019 (n =118), whose objective was to evaluate the response to the treatment and overall survival according to clinical, histopathological and treatment variables. The chi-square method was used for the association of variables. Overall survival was evaluated by the Kaplan Meier method and the Log-Rank and Breslow test for the comparison of the curves, with p <0.05. The disease control rate was 44.9. The median survival was 13.8 months (95 percent CI: 11.7-15.8). The statistically significant variables associated with greater response to treatment and survival were: no smoking habits; platelet-lymphocyte index below 200; T2-T3 primary tumors, predominantly located in the pancreatic head; no presence of metastases at diagnosis and greater than six doses of chemotherapy and Nimotuzumab. Patients classified as underweight and low serum albumin had worse survival (p <0.05). Second-line chemotherapy was performed in 42 patients and it was obtained SV of 17.4 months (95 percent CI: 13.5-21.4). Toxicities classified as grade 3-4 were reported in 27 patients (22.9 percent); the most frequently observed were: neuropathy (14.4 percent), neutropenia (10.2 perrcent) and thrombopenia (9.3 percent). Under clinical practice conditions, Nimotuzumab combined with GEMOX chemotherapy obtained optimal disease control and survival rates with a good safety profile(AU)

Clinical Observation of Nimotuzumab Combined with Docetaxel and Cisplatin in First-line Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma / 肿瘤防治研究

Objective To observe the efficacy and safety of nimotuzumab combined with docetaxel and cisplatin in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients. Methods We retrospectively analyzed the clinical data of recurrent or metastatic head and neck squamous cell carcinoma patients treated with nimotuzumab combined with docetaxel+cisplatin (observation group, n=28) and docetaxel+cisplatin (control group, n=30). We compared the ORR, DCR, PFS and OS between two regimens, and evaluated the safety. Results The ORR of observation and control groups were 42.9% and 16.7%, the DCR were 78.6% and 53.3%, and the median PFS were 6.2 and 4.3 months, respectively (all P < 0.05), and the median OS were 12.2 and 8.5 months (P > 0.05). There was no significant difference in adverse reactions between two groups (P > 0.05). Conclusion Compared with simple chemotherapy, nimotuzumab combined with docetaxel and cisplatin in the first-line treatment could improve the short-term clinical efficacy and prolong the progression-free survival of the patients with recurrent or metastatic head and neck squamous cell carcinoma, and caused no additional adverse reactions.

Nimotuzumab combinado con quimioradioterapia en pacientes con carcinoma epidermoide esofágico avanzado en el mundo real / Nimotuzumab combined with chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma in the real world

Introducción: La supervivencia global de pacientes con cáncer de esófago continúa siendo baja a pesar de los avances terapéuticos realizados en las últimas décadas. Objetivo: Evaluar respuesta al tratamiento y supervivencia global. Métodos: Se realizó un estudio retrospectivo y observacional en pacientes con carcinoma epidermoide esofágico avanzado, tratados con nimotuzumab combinado con quimioradioterapia, atendidos en el Servicio de Oncología Clínica del Hospital Ameijeiras, entre enero 2013 y junio de 2019 (n = 94). Se utilizó chi-cuadrado para la asociación de variables, con un valor p< 0,05. Se evaluó supervivencia global por el método de Kaplan Meier, y la prueba de Log-Rank para la comparación de las curvas. Resultados: La tasa de respuesta objetiva y de control de enfermedad fue 64,9 por ciento y 83 por ciento, respectivamente. El esquema de quimioterapia con cisplatino/fluouracilo fue el empleado con más frecuencia. Las variables con mayor respuesta y significación estadística fueron: ECOG cero, color de piel no blanca, tratamiento radiante ≥ 50 Gy, y más de catorce dosis de nimotuzumab. La mediana de supervivencia fue 13,03 meses (IC95 por ciento -10,9; 15,2), y las variables asociadas a una mayor probabilidad de supervivencia fueron: ECOG cero, dosis de quimioterapia > 75 por ciento de lo planificado, tratamiento radiante ≥ 50 Gy, más de catorce dosis de nimotuzumab, y alcanzar una respuesta objetiva (p< 0,05). Solo 5,8 por ciento de los pacientes presentaron toxicidades clasificadas como grado 3-5. Conclusiones: En condiciones de práctica clínica, este esquema de combinación obtuvo óptimas tasas de respuesta objetiva y supervivencia con buen perfil de toxicidad(AU)

Introduction: Overall survival of esophageal cancer patients remains low despite the therapeutic advances achieved in the last decades. Objective: Evaluate response to treatment and overall survival. Methods: An observational retrospective study was conducted of patients with advanced esophageal squamous cell carcinoma treated with nimotuzumab combined with chemoradiotherapy at the Clinical Oncology Service of Ameijeiras Hospital from January 2013 to June 2019 (n = 94). Association of variables was analyzed with the chi-square test, using a value of p < 0.05. Overall survival was evaluated with the Kaplan-Meier method, whereas the Log-Rank test was used to compare the curves. Results: Objective response and disease control rates were 64.9 percent and 83 percent, respectively. The chemotherapy scheme with cisplatin / fluorouracil was the most commonly applied. The variables with the greatest response and statistical significance were ECOG zero, skin color not white, radiation therapy ≥ 50 Gy and more than 14 doses of nimotuzumab. Median survival was 13.03 months (CI 95 percent -10,9; 15,2), whereas the variables associated to a greater probability of survival were ECOG zero, chemotherapy dose > 75% of plan, radiation therapy ≥ 50 Gy, more than 14 doses of nimotuzumab, and achieving an objective response (p< 0.05). Only 5.8 percent of the patients presented toxicities classified as grades 3-5. Conclusions: In clinical practice conditions, this combination scheme achieved optimum objective response and survival rates with a good toxicity profile(AU)

Research progress on application of nimotuzumab in esophageal cancer / 中华放射肿瘤学杂志

Esophageal cancer is a common malignant tumor of digestive system in China. Concurrent chemoradiotherapy has become the widely recognized method for the treatment of inoperable locally advanced esophageal carcinoma. Nevertheless, clinical efficacy of concurrent chemoradiotherapy remains to be enhanced. Nimotuzumab, the first human monoclonal antibody to treat malignant tumors in China, has been applied in the treatment of nasopharyngeal carcinoma, glioma, pancreatic cancer and other malignant tumors, which yields significant survival benefits and causes mild adverse events. Hence, more and more scholars are paying attention to its application value in the treatment of esophageal cancer. In this article, research progress on the application of nimotuzumab in esophageal cancer was reviewed, aiming to provide new ideas for the treatment of esophageal cancer.

Uso de nimotuzumab en paciente con astrocitoma anaplásico / Nimotuzumab in the treatment of a patient with anaplastic astrocytoma

Introducción: Nimotuzumab es una inmunoglobina de isotipo IgG1, obtenido por tecnología de ADN recombinante. La expectativa de vida de niños con tumores cerebrales recurrentes, refractarios a tratamientos a la cirugía, la radioterapia y la quimioterapia es de un mes aproximadamente. Con este tratamiento la supervivencia alcanza 44,5 meses. Objetivos: Presentar el caso clínico de un paciente con diagnóstico de Astrocitoma anaplásico que recibió tratamiento oncoespecífico concurrente con Nimotuzumab. Presentación de caso: Se realizó la descripción del diagnóstico, tratamiento y evolución de un paciente de 31 años de edad que fue diagnosticado con una neoplasia del sistema nervioso central. (Astrocitoma anaplásico). Recibió la combinación terapéutica de cirugía, radioterapia y anticuerpos monoclonales, lográndose una sobrevida de 39 meses. Conclusiones: La adición del anticuerpo monoclonal al tratamiento estándar de los tumores cerebrales aumentó la sobrevida del paciente, convirtiéndose en una alternativa terapéutica segura, ventajosa y factible como parte del tratamiento convencional en las condiciones asistenciales(AU)

Introduction: Nimotuzumab is an IgG1 isotype immunoglobin, obtained by recombinant DNA technology. Life expectancy is approximately one month in children with recurrent brain tumors, refractory to treatments to surgery, radiotherapy and chemotherapy. Survival reaches 44.5 months when using Nimotuzumab. Objectives: To report the clinical case of a patient diagnosed with anaplastic astrocytoma who received concurrent oncospecific treatment with Nimotuzumab. Case report: This paper describes the diagnosis, treatment and evolution of a 31-year-old male patient with neoplasm of the central nervous system (Anaplastic astrocytoma). He received the therapeutic combination of surgery, radiotherapy and monoclonal antibodies, achieving a survival of 39 months. Conclusions: The adding the monoclonal antibody to the standard treatment of brain tumors increased patient survival, making it a safe, advantageous and feasible therapeutic alternative as part of conventional treatment in healthcare conditions(AU)

Nimotuzumab y gemcitabina en el tratamiento del cáncer de páncreas y metástasis esplénica / Nimotuzumabe e gencitabina no tratamento do câncer de pâncreas e metástases esplênicas / Nimotuzumab and gemcitabine in the treatment of pancreatic cancer and splenic metastases

Se presentó un paciente masculino de 69 años con una colestasis extrahepática, pérdida de peso, astenia y anorexia, antecedentes de pancreatitis crónica, diabetes mellitus e hipertensión arterial, el cual fue diagnosticado con adenocarcinoma de páncreas con metástasis esplénica. Se le realizó colecistoyeyunostomía con yeyunoyeyunostomía por ser irresecable el tumor. Fue incluido en el ensayo clínico IIC RDEC166 y tratado con nimotuzumab y gemcitabina. En los estudios evolutivos no se apreciaron las imágenes metastásicas que se observaron antes del tratamiento lo que presupone la utilidad de estos fármacos para el control de éstas. No se encontraron referentes sobre el tema en la literatura nacional e internacional consultadas(AU)

A 69-year-old male patient presented with extrahepatic cholestasis, weight loss, asthenia and anorexia, a history of chronic pancreatitis, diabetes mellitus and arterial hypertension, who was diagnosed with adenocarcinoma of the pancreas with splenic metastases. A cholecystojejunostomy was performed with jejunum jejunostomy because the tumor was unresectable. It was included in the IIC RDEC166 clinical trial and treated with nimotuzumab and gemcitabine. In the evolutionary studies the metastatic images that were observed before the treatment were not appreciated, which presupposes the usefulness of these drugs for their control. No references on the subject were found in the national and international literature consulted(AU)

Paciente do sexo masculino, 69 anos, apresentou colestase extrahepática, perda de peso, astenia e anorexia, história de pancreatite crônica, diabetes mellitus e hipertensão arterial, diagnosticada com adenocarcinoma do pâncreas com metástases esplênicas. Uma colecistojejunostomia foi realizada com jejuno jejunostomia porque o tumor era irressecável. Foi incluído no ensaio clínico IIC RD-EC166 e tratado com nimotuzumab e gencitabina. Nos estudos evolutivos, as imagens metastáticas observadas antes do tratamento não foram apreciadas, o que pressupõe a utilidade desses medicamentos para seu controle. Não foram encontradas referências sobre o assunto na literatura nacional e internacional consultada(AU)

Nimotuzumab y radioterapia en el tratamiento de tumores del tallo cerebral en niños y adolescentes / Nimotuzumab and radiotherapy in the treatment of brainstem tumors in children and adolescents

Introducción: Los tumores localizados en el tallo cerebral en los niños y adolescentes conllevan un mal pronóstico, especialmente aquellos infiltrantes y difusos. Con el tratamiento de radioterapia apenas llegan a más de 15 por ciento de supervivencia y no mejora la cifra con quimioterapia agregada. Objetivos: Estimar el efecto de la asociación del tratamiento radiante con el anticuerpo monoclonal Nimotuzumab en la supervivencia de niños y adolescentes con tumores del tallo cerebral. Método: Estudio clínico no aleatorizado, analítico, longitudinal y prospectivo. Se estudió una serie de 46 pacientes entre 2 y 18 años de edad que padecían de tumores del tallo cerebral, infiltrantes y difusos, desde enero de 2008 y en seguimiento hasta marzo de 2018. Todos se trataron con radioterapia, con dosis entre 54 y 59,8 cGrey, dosis diaria de 1,8 cGrey, y se irradiaban de lunes a viernes. Mientras duró el tratamiento radiante recibieron Nimotuzumab, en la dosis de 150 mg/m2 de superficie corporal, luego semanal con 8 dosis, y finalmente mensual durante uno o dos años. Resultados: Se alcanzó en la serie una supervivencia media de 18,4 meses, y una esperada de 42,9 por ciento a 2 años y 35,5 por ciento a 5 años, estabilizada hasta los 10 años. Conclusiones: La combinación de radioterapia y el anticuerpo monoclonal Nimotuzumab incrementa la supervivencia en niños y adolescentes con tumores del tallo cerebral y es bien tolerada, aun en periodos prolongados, e incluso en casos de recidiva(AU)

Introduction: Tumors localized in the brainstem of children and adolescents entail a bad prognosis, especially those that are intrinsic and diffuse. With radiotherapy treatment, patients barely get a 15 percent of survival, and the numbers don't improve with added chemotherapy. Objectives: To estimate the effect of the association of radiotherapy treatment with Nimotuzumab monoclonal antibody in the survival of children and adolescents with brainstem tumors. . Method: Non randomized, analytical, longitudinal and prospective clinical study that was authorized by the National Regulatory Authority. There was studied a group of 46 patients aged from 2 to 18 years that suffered from intrinsic and diffuse brainstem tumors, from January 2008 (and in follow up) to March 2018. All the patients were treated with radiotherapy, with doses among 54 and 59,8 Grey, daily doses of 1,8 Grey, and from Monday to Friday. While they were under radiotherapy treatment, they get Nimotuzumab, in doses of 150 mg/m2 of corporal surface; then weekly doses of 8 shots; and finally, monthly doses during one or two years. Results: In this group there was a survival mean of 18, 4 months, and an expected survival of 42, 9 percent for 2 years and 35, 5 percent for 5 years that can be stabilized to 10 years. Conclusions: Combination of radiotherapy and Nimotuzumab monoclal antibody can increase the survival from brainstem tumors in children and adolescents(AU)

Evaluación del perfil de seguridad del racotumomab y nimotuzumab en pacientes con cáncer de pulmón de células no pequeñas / Evaluation of the safety profile of racotumomab and nimotuzumab in patients with non-small cell lung cancer

RESUMEN Fundamento: El cáncer de pulmón de células no pequeñas es el cáncer de origen epitelial que más muertes provoca; por lo que el estudio de nuevas terapias es una prioridad investigativa en Cuba; para ello se realizaron estudios multicéntricos que evaluaron entre otros aspectos, el perfil de seguridad del nimotuzumab y racotumomab, anticuerpos monoclonales de origen cubano en el tratamiento de esta enfermedad. Objetivo: Evaluar el perfil de seguridad del nimotuzumab y racotumomab en pacientes con cáncer de pulmón de células no pequeñas avanzado después de la primera línea de tratamiento oncoespecífico. Metodología: Se diseñó un estudio multicéntrico, prospectivo, longitudinal en 32 pacientes adultos con cáncer de pulmón de células no pequeñas avanzado después de la primera línea del tratamiento oncoespecífico en la provincia Sancti Spíritus entre junio del 2014 a junio del 2015. Resultados: De los 6 pacientes que recibieron nimotuzumab y 26 pacientes que recibieron racotumomab, en estadio tumoral IIIB o IV, el 75 % entró al estudio con buen estado clínico. El 66 % de ellos no presentó efectos adversos, entre los que se presentaron está, dolor en el sitio de inyección, torácico y la fiebre, todos de intensidad leve o moderada. No se encontraron diferencias significativas entre las proporciones de eventos adversos leves en ambos grupos de sujetos. No se reportaron eventos adversos severos. Todos los eventos se clasificaron en no serios, no graves y del 98.33 % de ellos el paciente se recuperó sin ayuda médica. Conclusiones: Los resultados sugieren que los productos empleados son seguros, expresado en la baja frecuencia de aparición de eventos adversos, la generalidad de ellos leves no graves/no serios, sin que dejaran secuela en los pacientes.

ABSTRACT Background: Non-small cell lung cancer is the cancer of epithelial origin that causes most of deaths; so the study of new therapies is a research priority in Cuba; thus, multicenter studies are carried out which evaluate, among other aspects, the safety profile of nimotuzumab and racotumomab, monoclonal antibodies of Cuban origin in the treatment of this disease. Objective: To evaluate the safety profile of nimotuzumab and racotumomab in patients with advanced non-small cell lung cancer after the first-line of oncospecific treatment. Methodology: A multicenter, prospective, longitudinal study was designed in 32 adult patients with advanced non-small cell lung cancer after the first-line of oncospecific treatment in Sancti Spíritus province from June 2014 to June 2015. Results: The six patients who received nimotuzumab and the twenty-six patients who received racotumomab, in tumor stage IIIB or IV, 75 % participated in the study with good clinical conditions. The 66% of them did not present adverse effects, among which there were, pain at the location of injection, thoracic pain and fever, all of mild or moderate intensity. No significant differences were found between the proportions of mild adverse events in both groups of subjects. No severe adverse events were reported. All events were classified as non-serious, non-very serious and 98.33 % of them recovered without medical help. Conclusions: The results suggest that the products used are safe, expressed in the low frequency of occurrence of adverse events, the generality of them mild non-very serious / non-serious, without no sequel in patients.

Características humorales de los tumores de cabeza y cuello en pacientes tratados con nimotuzumab / Humoral characteristics of head and neck tumors in patients treated with nimotuzumab

Se efectuó un estudio observacional, descriptivo y retrospectivo de 36 pacientes incluidos en el ensayo clínico (fase IV) Seguridad y efectividad del nimotuzumab en tumores de cabeza y cuello, desarrollado en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde enero de 2013 hasta diciembre de 2016, con vistas a identificar las características humorales de dichos tumores en los afectados. Se utilizó la prueba t de Student con una significación estadística de p <0,05. Predominaron el sexo masculino en mayores de 60 años de edad, los efectos adversos clínicos y el tumor de faringe; el estadio clínico III y el carcinoma epidermoide bien diferenciado fueron los más frecuentes. No existieron diferencias estadísticamente significativas entre los parámetros de laboratorio antes del tratamiento combinado con nimotuzumab y durante este. Dicho medicamento constituyó una alternativa terapéutica segura, ventajosa y factible como parte del plan terapéutico convencional en las condiciones asistenciales

An observational, descriptive and retrospective study of 36 patients included in the (phase IV) clinical trial Security and effectiveness of nimotuzumab in head and neck tumors was carried out. It was developed at Conrado Benítez Oncological Hospital in Santiago de Cuba, from January, 2013 to December, 2016, aimed at identifying the humoral characteristics of these tumors in the affected patients. The Student t test was used with a statistical significance of p <0.05. There was a prevalence of the male sex in older than 60 years, the clinical adverse effects and the pharynx tumor; the clinical stage III and the well differentiated epidermoid carcinoma were the most frequent findings. There were no statistically significant differences among the laboratory parameters before and during the combined treatment with nimotuzumab. This medication constituted a sure, advantageous and feasible therapeutic alternative as part of the conventional therapeutic plan in assistance conditions

Supervivencia libre de progresión en pacientes portadores de meningiomas vacunados con nimotuzumab / Progression free survival in patients with meningioma which got Nimotuzumab vaccine

Introducción: en los últimos años la biología de los meningiomas cerebrales ha comenzado a entenderse mejor. La inmunoterapia activa contra el factor de crecimiento epidérmico es un concepto emergente, en el que se propone manipular la respuesta inmune del individuo, para generar anticuerpos específicos contra el factor de crecimiento epidérmico, capaces de bloquear la unión ligando-receptor y por consiguiente la señalización a través de este último. El receptor del factor de crecimiento epidérmico está sobrexpresado en este tipo de tumor. Objetivo: estimar la sobrevida libre de progresión de la entidad clínica y su relación con algunas variables socio-demográficas y terapéuticas seleccionadas. Métodos: se realizó un estudio descriptivo, transversal, en 25 pacientes portadores de meningiomas, tratados con un anticuerpo monoclonal humanizado (AcM h-R3) (nimotuzumab), en el Hospital Provincial Docente Clínico Quirúrgico Saturnino Lora de Santiago de Cuba, en el período comprendido entre el 1 de diciembre del 2013 y el 30 de noviembre del 2015. Resultados: el conjunto de pacientes incluidos en el estudio (n= 25) se caracterizó por el predominio del sexo femenino (60 por ciento), edad de 50 y más años (68 por ciento), piel blanca (48 por ciento) y escala de Karnofsky de 100 puntos (84 por ciento). El tiempo medio libre de progresión fue de 17 ± 8,6 meses. Conclusiones: fueron identificadas las principales características de la supervivencia libre de progresión del meningiomas en pacientes vacunados con AcM h-R3 y el tiempo fue como promedio de alrededor de año y medio(AU)

Introduction: in recent years the biology of brain meningiomas has begun to be better understood. Active immunotherapy against epidermal growth factor is an emerging concept, in which it is proposed to manipulate the immune response of the individual, to generate specific antibodies against epidermal growth factor, capable of blocking the ligand / receptor binding and therefore signaling through the latter. The epidermal growth factor receptor is overexpressed in this type of tumor. Objective: to estimate the progression free survival and its relation with some selected socio-demographic and therapeutic variables. Methods: a descriptive, cross-sectional study was conducted in 25 patients with meningiomas, treated with a humanized monoclonal antibody (mAb h-R3) (Nimotuzumab), in the Provincial Clinical-Surgical Teaching Hospital Saturnino Lora of Santiago de Cuba, from December 1, 2013 to November 30, 2015. Results: the group of patients included in the study (n= 25), was characterized by the predominance of females (60 percent), age 50 and over (68 percent), white skin (48 percent) and Karnofsky scale of 100 points (84 percent). The mean progression-free time was 17 ± 8.6 months. Conclusions: the main characteristics of progression-free survival of meningiomas were identified in patients vaccinated with mAb h-R3 and the progression-free time reached almost of a year and a half(AU)

Aplicación de productos inmunoterapéuticos en ensayos clínicos oncológicos en Santiago de Cuba / Implementation of immunotherapeutical products in cancer clinical trials in Santiago de Cuba

Se realizó un estudio descriptivo y retrospectivo sobre la conducción de ensayos clínicos durante 23 años en Santiago de Cuba, con el objetivo de describir la aplicación de 3 productos inmunoterapéuticos (CIMAher-Nimotuzumab, CIMAvax-EGF y Vaxira-Racotumomab) para el tratamiento de pacientes con cáncer en hospitales y policlínicos de la provincia. Se revisaron los informes finales de dichos ensayos, así como la información disponible del centro promotor desde 1992 hasta 2015. Se ejecutaron 20 protocolos de ensayos clínicos por 500 investigadores de 25 especialidades, distribuidos en 4 hospitales de la provincia y 2 se extendieron a 4 áreas de atención primaria de salud. Se concluyó que la aplicación de estos productos inmunoterapéuticos contribuyó al registro sanitario de estos, lo cual enriqueció el arsenal terapéutico para los afectados por cáncer en Santiago de Cuba, con un elevado impacto social

A retrospective descriptive study on the presentation of clinical trials was carried out during 23 years in Santiago de Cuba, with the objective of describing the implementation of 3 immunotherapeutical products (CIMAher-Nimotuzumab, CIMAvax-EGF and Vaxira-Racotumomab) for the treatment of patients with cancer in hospitals and polyclinics from the province. The final reports of each clinical trial and the available information of the promoter center were reviewed from 1992 to 2015. Twenty protocols of clinical trials were implemented by 500 investigators of 25 specialties distributed in 4 hospitals of the province and 4 primary health care areas, where 2 clinical trials in patients with lung cancer were carried out. It was concluded that the implementation of these immunotherapeutical products contributed to the health registration of them, enriching the therapeutic arsenal for the treatment of patients with cancer in Santiago de Cuba, with a high social impact

Curative effect of nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal carcinoma / 中国基层医药

Objective To study the clinical efficacy of nimotuzumab combined with concurrent chemoradio therapy in the treatment of locally advanced esophageal carcinoma . Methods 80 patients with locally advanced esophageal carcinoma were selected as subjects. They were divided into the control group and the treatment group according to the random number table method, with 40 cases in each group. The control group was treated with docetaxel plus cisplatin(TP) chemotherapy combined with radiotherapy,and the treatment group was treated with nimotuzumab combined with concurrent chemoradiotherapy. 21 days for a period of treatment and the two groups were treated for 3 periods. The clinical efficacy of the two groups after treatment was evaluated and compared. The serum carbohydrate antigen 125 ( CA125 ) , carbohydrate antigen 199 ( CA199 ) , carbohydrate antigen 724 ( CA724 ) , carcinoembryonic antigen( CEA) and squamous cell carcinoma antigen( SCC) levels of the two groups before and after treatment were calculated and compared. The incidence rate of adverse reactions, including radioactive esophagitis, radioactive pneumonia,hematology toxicity and allergic reaction were calculated and compared between the two groups during the treatment. Results The effective rate of the treatment group was 80. 00%,which was significantly higher than 57. 50% of the control group(χ2 =4. 713,P=0. 030). The serum CA125,CA199,CA724,CEA and SCC levels of the treatment group after treatment were (30. 18 ± 4. 14) U/mL,(32. 42 ± 3. 67) U/mL,(7. 48 ± 1. 12) U/mL, (11. 68 ± 2. 02 )μg/L, ( 0. 73 ± 0. 17 ) ng/mL, which were significantly lower than those of the control group [(44.27 ±6. 42) U/mL,(53. 93 ± 5. 17) U/mL,(15. 03 ± 2. 54) U/mL,(25. 22 ± 3. 27)μg/L,(1. 61 ± 0. 28)ng/mL](t=11. 665,21. 457,17. 201,22. 280,16. 991,all P<0. 05). There were no significant differences in the incidence rates of adverse reactions, including the radioactive esophagitis, radioactive pneumonia, hematology toxicity and allergic reaction (7. 50% vs. 10. 00%,10. 00% vs. 12. 50%,2. 50% vs. 5. 00%,12. 50% vs. 15. 00%) between the two groups(χ2 =0. 157,0. 125,0. 346,0. 105,all P>0. 05). Conclusion Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal carcinoma has remarkable clinical efficacy and good safety,which can significantly reduce the serum CA125,CA199,CA724,CEA and SCC levels,and it is worthy of clinical application.

Clinical efficacy and prognosis of nimotuzumab combined with intensity modulated radiotherapy for advanced local nasopharyngeal carcinoma / 中国基层医药

Objective To observe the clinical efficacy and prognosis of nimotuzumab combined with intensity modulated radiotherapy(IMRT) in the treatment of advanced local nasopharyngeal carcinoma.Methods 82 patients with advanced nasopharyngeal carcinoma were selected, and they were randomly divided into observation group(40 cases) and control group(42 cases) according to the digital table.The observation group was treated with nimotuzumab plus IMRT plus cisplatin, and the control group was treated with IMRT plus cisplatin.After 7 weeks of treatment, the clinical efficacy, adverse reactions and T cell subsets were observed.And the patients were followed up for 1 year, 2 years and 3 years to evaluate the survival rate.Results In the observation group, the total remission rate was 75.00%,which was higher than that in the control group(59.09%),the difference was statistically significant(x2=35.81,P<0.05).The CD+4,CD+8 and CD+4/CD+8 levels in the observation group were similar to those in the control group(tCD+4=0.59,P=0.56;tCD+8=1.70,P=0.01;tCD+4/CD+8=0.13,P=0.89).The incidence rates of Ⅰ degree and Ⅱ degree mucosal reaction and dermatitis in the observation group were 35.00%,40.00%,40.00%,35.00%,respectively,which were higher than 9.09%,9.09%,9.09%,9.09% of the control group,the differences were statistically significant(x2Ⅰmucous membrane=4.18,P=0.04;x2Ⅱmucous membrane=5.52,P=0.02;x2Ⅰdermatitis=5.52,P=0.02;x2Ⅱdermatitis=4.18,P=0.04).The 2-year and 3-year survival rates in the observation group were 65.50%,60.00%,respectively,which were significantly higher than 31.82%,27.27% in the control group, the differences were statistically significant(x2=4.11,P=0.04;x2=4.58,P=0.03).Conclusion Nimotuzumab combined with IMRT in the treatment of advanced nasopharyngeal carcinoma has good short-term clinical efficacy, good long-term efficacy and controllable adverse reactions.It is worthy of clinical application.

Curative effect of nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal carcinoma / 中国基层医药

Objective To study the clinical efficacy of nimotuzumab combined with concurrent chemoradio therapy in the treatment of locally advanced esophageal carcinoma . Methods 80 patients with locally advanced esophageal carcinoma were selected as subjects. They were divided into the control group and the treatment group according to the random number table method, with 40 cases in each group. The control group was treated with docetaxel plus cisplatin(TP) chemotherapy combined with radiotherapy,and the treatment group was treated with nimotuzumab combined with concurrent chemoradiotherapy. 21 days for a period of treatment and the two groups were treated for 3 periods. The clinical efficacy of the two groups after treatment was evaluated and compared. The serum carbohydrate antigen 125 ( CA125 ) , carbohydrate antigen 199 ( CA199 ) , carbohydrate antigen 724 ( CA724 ) , carcinoembryonic antigen( CEA) and squamous cell carcinoma antigen( SCC) levels of the two groups before and after treatment were calculated and compared. The incidence rate of adverse reactions, including radioactive esophagitis, radioactive pneumonia,hematology toxicity and allergic reaction were calculated and compared between the two groups during the treatment. Results The effective rate of the treatment group was 80. 00%,which was significantly higher than 57. 50% of the control group(χ2 =4. 713,P=0. 030). The serum CA125,CA199,CA724,CEA and SCC levels of the treatment group after treatment were (30. 18 ± 4. 14) U/mL,(32. 42 ± 3. 67) U/mL,(7. 48 ± 1. 12) U/mL, (11. 68 ± 2. 02 )μg/L, ( 0. 73 ± 0. 17 ) ng/mL, which were significantly lower than those of the control group [(44.27 ±6. 42) U/mL,(53. 93 ± 5. 17) U/mL,(15. 03 ± 2. 54) U/mL,(25. 22 ± 3. 27)μg/L,(1. 61 ± 0. 28)ng/mL](t=11. 665,21. 457,17. 201,22. 280,16. 991,all P<0. 05). There were no significant differences in the incidence rates of adverse reactions, including the radioactive esophagitis, radioactive pneumonia, hematology toxicity and allergic reaction (7. 50% vs. 10. 00%,10. 00% vs. 12. 50%,2. 50% vs. 5. 00%,12. 50% vs. 15. 00%) between the two groups(χ2 =0. 157,0. 125,0. 346,0. 105,all P>0. 05). Conclusion Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced esophageal carcinoma has remarkable clinical efficacy and good safety,which can significantly reduce the serum CA125,CA199,CA724,CEA and SCC levels,and it is worthy of clinical application.