Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Este documento é uma versão resumida do relatório técnico da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ Conitec e foi elaborado numa linguagem simples, de fácil compreensão, para estimular a participação da sociedade no processo de Avaliação de Tecnologias em Saúde (ATS) que antecede a incorporação, exclusão ou alteração de medicamentos, produtos e procedimentos utilizados no SUS. As recomendações da Comissão são submetidas à consulta pública pelo prazo de 20 dias. Após analisar as contribuições recebidas na consulta pública, a Conitec emite a recomendação final, que pode ser a favor ou contra a incorporação, exclusão ou alteração da tecnologia analisada. A recomendação final é, então, encaminhada ao Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde -SCTIE/MS, que decide sobre quais tecnologias em saúde serão disponibilizadas no SUS

Cabozantinibe ou nivolumabe para o tratamento de segunda linha para pacientes com carcinoma de células renais metastático / Cabozantinib or nivolumabe for second-line treatment for patients with metastatic renal cell carcinoma

Relatório técnico com Leis que estabelece que a incorporação, a exclusão ou a alteração de novos medicamentos, produtos e procedimentos, bem como a constituição ou alteração de protocolo clínico ou de diretriz terapêutica são atribuições do Ministério da Saúde (MS). A estrutura de funcionamento da Conitec é composta por Plenário e Secretaria-Executiva. A gestão e a coordenação das atividades da Conitec, bem como a emissão do relatório de recomendação sobre as tecnologias analisadas são de responsabilidade da Secretaria-Executiva ­ exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE/MS).

Influence of treatment access on survival of metastatic renal cell carcinoma in brazilian cancer center

ABSTRACT Background: Tyrosine kinase inhibitors (TKI) and immunotherapy improved survival in metastatic renal cell carcinoma (mRCC). Disparities in treatment access are present in healthcare systems globally. The aim of this study was to analyze survival outcomes of mRCC patients treated with first-line TKIs in the public (PHS) and private (PrS) health system in a Brazilian Cancer Center. Materials and Methods: Records from all mRCC patients treated with first-line TKIs from 2007-2018 were reviewed retrospectively. Categorial variables were compared by Fisher's exact test. Survival was estimated by Kaplan-Maier method and survival curves were compared using the log-rank test. Prognostic factors were adjusted by Cox regression model. Results: Of the 171 eligible patients, 37 (21.6%) were PHS patients and 134 (78.4%) were PrS patients. There were no difference in age, gender, or sites of metastasis. PHS patients had worse performance status (ECOG ≥2, 35.1% vs. 13.5%, p=0.007), poorer risk score (IMDC poor risk, 32.4% vs. 16.4%, p=0.09), and less nephrectomies (73% vs. 92.5%, p=0.003) than PrS patients. Median lines of therapy was one for PHS versus two for PrS patients (p=0.03). Median overall survival (OS) was 16.5 versus 26.5 months (p=0.002) and progression-free survival (PFS), 8.4 versus 11 months (p=0.01) for PHS and PrS patients, respectively. After adjusting for known prognostic factors on multivariate analysis, PHS patients still had a higher risk of death (HR: 1.61, 95% CI: 1.01-2.56, p=0.047). Conclusion: Patients with mRCC treated via the PHS had worse overall survival, possibly due to poorer prognosis at presentation and less drug access.

Expert consensus on diagnosis and treatment of renal cell cancer bone metastasis (2021 edition) / 中华肿瘤杂志

Bone is a common metastatic site of renal cell carcinoma (RCC), with about 30% of metastatic RCC patients are suffering from bone metastasis. More than 70% of RCC patients with bone metastasis may experience skeletal related events (SREs), which may severely impair patients' quality of life and even shorten their survival time. Therefore, SREs prevention has become one of the treatment objectives of RCC bone metastasis. Bone-modifying agents are the basic treatment of bone metastases in addition to anti-tumor therapy. The treatment of RCC bone metastasis also requires multi-disciplinary team and individualized comprehensive treatment strategies. To standardize the diagnosis and treatment of RCC bone metastasis in China, the expert group of Genitourinary Oncology Committee, Chinese Anti-cancer Association has formulated the expert consensus for the reference of clinical practice, to improve the general therapeutic level of RCC with bone metastasis and benefit more patients.

Clinicopathological characteristics of surgically treated localized renal masses in patients previously exposed to chemotherapy

ABSTRACT Purpose: To explore the potential association between renal mass characteristics and a history of chemotherapy. Materials and methods: A retrospective review of records of patients surgically treated for a localized renal mass between 2000 and 2012 was undertaken following an institutional review board approval. Patients age and sex, renal mass clinical characteristics (radiological size and mode of presentation) and pathological characteristics (diagnosis, renal cell carcinoma subtype, Fuhrman grade and stage) were compared between patients with and without a history of chemotherapy, using Fisher's exact test, Student's t-test and Wilcoxon rank sum test. A multivariate logistic analysis was performed to evaluate the independent association of chemotherapy and tumor pathology. Results: Of the 1,038 eligible patients, 33 (3%) had a history of chemotherapy. The distribution of clinical stage, renal mass diagnosis, renal cell carcinoma subtype, Fuhrman grade, pathological stage, sex and median age were similar between the general population and the chemotherapy group. However, the latter had a higher rate of incidental presentation (P = 0.003) and a significantly smaller median radiological tumor size (P = 0.01). In a subset analysis of T1a renal cell carcinoma, the chemotherapy group presented an increased rate of high Fuhrman grade (P = 0.03). On multivariate analysis adjusted for radiological tumor size, sex and age the chemotherapy cohort had a 3.92 higher odds for high Fuhrman grade. Conclusion: Patients with a history of chemotherapy typically present with smaller renal masses that, if malignant, have higher odds of harboring a high Fuhrman grade and thus may not be suitable for active surveillance.

Prognostic significance of the dynamic changes of systemic inflammatory response in metastatic renal cell carcinoma

ABSTRACT Purpose: To elucidate the prognostic value of systemic inflammatory response in patients with metastatic renal cell carcinoma (mRCC) who are treated with sunitinib, we evaluated the prognostic role of C-reactive protein (CRP) kinetics. This study also compared prognostic models containing CRP kinetics and neutrophil-to-lymphocyte ratio (NLR) kinetics. Materials and Methods: A consecutive cohort of 94 patients with mRCC who were treated with sunitinib was retrospectively included from Fudan University Shanghai Cancer Center. According to dynamic changes in CRP and the NLR, patients were divided into three groups for analysis of CRP and NLR kinetics. The associations between survival and potential prognostic factors were assessed. The incremental value of prognostication was evaluated. Results: A significant difference (P<0.001) in overall survival (OS) was observed among the three groups of CRP kinetics. The median OS of the non-elevated group was nearly 1.3-fold longer than that of the normalized group (33.0 vs. 26.3 months), and two times longer than that of the non-normalized group (33.0 vs. 14.0 months). Multivariate analysis showed that CRP and NLR kinetics were independent prognostic indicators. The model containing CRP kinetics had a better predictive accuracy than that with NLR kinetics, which was supported by the C-index (0.731 vs. 0.684) and the likelihood ratio χ2 test (79.9% vs. 44.9%). Conclusion: Our study suggests that dynamic changes in CRP can better predict survival in patients with mRCC who are treated with sunitinib. Routine assessment of CRP before and after targeted therapy would help identify patients at risk of a poor outcome.

Efficacy of targeted therapy for advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

ABSTRACT We conducted a systematic review and meta-analysis of the literature on the efficacy of the targeted therapies in the treatment of advanced RCC and, via an indirect comparison, to provide an optimal treatment among these agents. A systematic search of Medline, Scopus, Cochrane Library and Clinical Trials unpublished was performed up to Jan 1, 2015 to identify eligible randomized trials. Outcomes of interest assessing a targeted agent included progression free survival (PFS), overall survival (OS) and objective response rate (ORR). Thirty eligible randomized controlled studies, total twentyfourth trails (5110 cases and 4626 controls) were identified. Compared with placebo and IFN-α, single vascular epithelial growth factor (receptor) tyrosine kinase inhibitor and mammalian target of rapamycin agent (VEGF(r)-TKI & mTOR inhibitor) were associated with improved PFS, improved OS and higher ORR, respectively. Comparing sorafenib combination vs sorafenib, there was no significant difference with regard to PFS and OS, but with a higher ORR. Comparing single or combination VEGF(r)-TKI & mTOR inhibitor vs BEV + IFN-α, there was no significant difference with regard to PFS, OS, or ORR. Our network ITC meta-analysis also indicated a superior PFS of axitinib and everolimus compared to sorafenib. Our data suggest that targeted therapy with VEGF(r)-TKI & mTOR inhibitor is associated with superior efficacy for treating advanced RCC with improved PFS, OS and higher ORR compared to placebo and IFN-α. In summary, here we give a comprehensive overview of current targeted therapies of advanced RCC that may provide evidence for the adequate targeted therapy selecting.

Eficacia y seguridad de sunitinib para el tratamiento de pacientes adultos con cáncer renal de células no claras (cromófobo) con enfermedad metastásica irresecable / Efficacy and safety of sunitinib for the treatment of adult patients with non-clear cell (chromophobe) kidney cancer with unresectable metastatic disease

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnologia de la eficacia y seguridad de sunitinib para el tratamiento de pacientes adultos con cáncer renal de células no claras (cromófobo) con enfermedad metastásica irresecable. Aspectos Generales: El carcinoma de células renales (CCR) usualmente se origina en el revestimiento de los túbulos del riñon y contiene muchos vasos sanguíneos. El CCR es el tipo más común de cáncer de riño, representando el 90% de todos los cánceres de riños y aproximadamente el 3% de todos los cánceres en adultos en Europa. Tecnología Sanitaria de Interés: Sunitinib es un fármaco antineoplásico de administración oral, que inhibe múltiples receptores de tirosina quinasa (RTKs), algunos de los cuales están implicados en el crecimiento tumoral, la neoangiogénesis y la progresión a metástasis. Estos incluyen los receptores del factor de crecimiento derivado de plaquetas (PDGFR alfa y PDGFR beta), factor de crecimiento del endotelio vascular (VEGFR1, (VEGFR2 y (VEGFR3), factor de células madre (KIT), tirosin-kinasa 3tipo Fms (FLT3), factor estimulador de colonias (CSF-1R) y factor neurotrófico derivado de la línea celular glial (RET). La inhibición simultánea de estos receptores genera una fuerte disminución de la neovascularización tumoral, conllevando así a la reducción del tumor, y a su vez explica muchos de sus efectos adversos tales como el síndrome mano pie, estomatitis, y otra variedad de efectos dermatológicos. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda sistemática de la evidencia científica, especialmente la proveniente de ensayos clínicos, con respecto a la eficacia y seguridad de sunitinib en pacientes adultos con diagnóstico de carcinoma de células renales metastásico cromófobo en las bases de datos MEDLINE, TRIPDATABASE y LILACS. Una vez identificados los artículos que respondían a la preginta PICO, se pasó a revisar la bibliografia incluida en dichos artículos seleccionados, con la finalidad de identificar evidencia adicional. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica tales como National Comprehensive Cancer Network (NCCN), The National Guideline for Clearinghouse (NGC), Scottish Intercollegiate Guidelines Network (SIGN), The National Institute for Health and Cares Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH), The Agency for Healthcarre Research and Quality (AHQR) y The Cochrane Collaboration. Se hizo una búsqueda adicional en clinicaltrials.gov y www.ensayosclinicos-repec.ins.gob.pe, para poder identificar ensayos clínicos en curso o que no hayan sido publicados. RESULTADOS: Sinopsis de la Evidencia: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de sunitinib, en comparación a la mejor terpia de soporte, como tratamiento del cáncer renal de céluas no claras de tipo cromófobo con enfermedad metastásica irresecable. Debido a que no se encontraron ensayos clínicos que respondieran a la preginta PICO, se incluyeron diseños de estudios del tipo ensayos clínicos de un solo brazo, ensayos clínicos comparativos versus otras terapias dirigidas y estudios retrospectivos. CONCLUSIONES: A la fecha, no existe evidencia suficiente sobre la eficacia de sunitinib, con respecto a la mejor terpia de soporte, en pacientes adultos con diagnóstico de cáncer renal cromófobo, en términos de mayor sobrevida global, calidad de vida, sobrevida libre de progresión y tasa respuesta objetiva. El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) no aprueba el uso de sunitinib para el tratamiento de pacientes adultos con cáncer de células no claras (cromófobo) con enfermedad metastásica irresecable.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Seguridad y eficacia del sorafenib en el carcinoma renal metastasico avanzado que progresa despues del tratamiento de primera linea con sunitinib / Safety and efficacy of sorafenib in advanced metastatic renal cell carcinoma progressing after first-line treatment with sunitinib

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del medicamento sorafenib a su uso, en pacientes con carcinoma renal metastásico que progresa al tratamiento de primera línea con sunitinib. Aspectos Generales: El carcinoma de células renales (CCR) es un tipo de cáncer del riñon que se origina en las células de los túbulos renales y contienen muchos vasos sanguíneos. El CCR es responsable del 80 al 85% de las neoplasias renales primarias. Cerca del 8% del resto de las otras neoplasias provienen de las células transicionales de la pelvis renal. Tecnología Sanitaria de Interés: Sorafenib: Sorafenib es un inhibidor multiquinasa que inhibe el desarrollo de los vasos sanguíneos del tumor y la proliferación de las células tumorales. Esta droga tiene una acción dual, inhibiendo la casa cascada raf y los receptores de los factores de crecimiento derivado de plaquetas (PDGF) y de crecimiento endotelial vascular (VEGF), presentes en las células tumorales, en las células endoteliais y en los pericitos. El Sorafenib está autorizado para el tratamiento de pacientes con CCR avanzado en quienes el tratamiento con Interferón alfa o interleuquina-2 han fallado o está contraindicado. Sorafenib se administra oralmente con dosis recomendadas para el CCR avanzado de 400 mg dos veces al día. El tratamiento debe interrumpirse cuando aparezcan eventos adversos inaceptables para el paciente. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del sorafenib como tratamiento de segunda línea en pacientes con CCRm o avanzado progresivo a un tratameinto de primera líena con sunitinib, en las bases de datos de OVID MEDLINE y TRIPDABASE. También se hizo una búsqueda adicional en www.clinicals.ogv, para poder identificar ensayos en desarrollo. Adicionalmente, se hizo una búsqueda dentro de la inforamción generada por grupos que realizan revisiones sistemáticas, evalución de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excelence (NICE) y la European Society for Medical Oncology (ESMO). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso de sorafenib como tratamiento de segunda línea en pacientes con CCRM que progresaron a pesar del tratamiento de primera línea con sunitinib. Solo se identificaron dos GPC que cumplieram los criterios de elegibilidad. CONCLUSIONES: no se ha encontrado evidencia respecto al beneficio y riesgo del uso de sorafenib como tratamiento de segunda línea en pacientes con CCRm que progresan después del tratamiento con sunitinib, respecto al tratamiento de soporte o placebo. Las guías identificadas en esta evaluación recomiendan el uso de sorafenib solo en pacientes que progresan después de recibir tratamiento a base de citoquinas, pero no está incluido en las recomendaciones si el paciente progreso después de recibir medicamentos dirigidos a VEGF. Otros medicamentos diferentes a sorafenib vienen siendo evaluados en pacientes con CCRm progresaron después de recibir medicamentos a los VEGF. Dado que no existe evidencia que responda a la pregunta PICO de esta evaluación, el Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso de sorafenib para el tratamiento de pacientes con CCRm que progresarion después del tratamiento con sunitinib.

Eficacia y seguridad de pazopanib en comparacion con sunitinib en pacientes con diagnóstico de carcinoma renal de élulas claras metastásico sin tratamiento previo, ecog 0-1 y factor de riesgo intermedio o bajo MSKCC / Efficacy and safety of pazopanib compared to sunitinib in patients with clear metastatic renal cell carcinoma without previous treatment, echocardiography 0-1 and intermediate or low risk factor MSKCC

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del medicamento pazopanib respecto a su uso en pacientes con carcinoma renal de células claras metastásico que no hayan recibido tratamiento previo. Aspectos Generales: El carcinoma de células renales (RCC) representa el 2-3% de todas las neoplasias malignas a nivel mundial, siendo la séptima causa más común de cáncer en varones y la novena causa más común en mujeres. En el Perú, el 1.7% de todos los casos de cáncer reportados entre el 2006 y el 2011 fueron de origen renal(3). El carcinoma renal de células claras representa el 65-90% de todos los RCC por lo que la mayor parte de estudios en RCC se hacen tomando como referencia a esta población. La aparición de RCC se ha asociado a factores como el tabaquismo, obesidad, insuficiencia renal crónica terminal, enfermedad quística renal adquirida, esclerosis tuberosa y la edad avanzada. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de \r\npazopanib en comparación con sunitinib sobre la sobrevida global, sobrevida libre de enfermedad, calidad de vida, perfil de eventos adversos y tasa de respuesta objetiva de pacientes con carcinoma renal de células claras metastásico sin tratamiento previo, ECOG 0-1 y factor de riesgo intermedio o bajo MSKCC en las bases de datos MEDLINE. Se hizo una búsqueda adicional en www.clinicaltrials.gov, para poder identificar ensayos aun en elaboración o que no hayan sido publicados. Adicionalmente, se hizo una búsqueda dentro de la información generada por grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The National Guideline for Clearinghouse. Por último, también se buscaron GPC y \r\npublicaciones en grupos dedicados a la educación, investigación y mejora en la práctica clínica oncológica, tales como The National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO) y European Society of Medical Oncology (ESMO). RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de pazopanib como tratamiento de primera línea para pacientes con diagnóstico de RCC de células claras metastásico sin tratamiento previo, en comparación con sunitinib. Se presenta la evidencia simplificada y correspondiente a guías de práctica clínica, revisiones sistemáticas y meta-análisis de los últimos 3 años; así como los ensayos clínicos con fecha de publicación posterior a las revisiones sistemáticas incluidas. CONCLUSIÓN: De acuerdo a la revisión de las información científica existente, se concluye que el fármaco pazopanib administrado en dosis de 800mg vía oral por día es \r\nuna intervención equivalente a sunitinib para el tratamiento de primera línea de pacientes con carcinoma renal de células claras sin tratamiento previo, de pronóstico bueno o intermedio según el score MSKCC y ECOG 0-1. Los estudios muestran que pazopanib no es inferior a sunitinib respecto a variables de eficacia como sobrevida global, la sobrevida libre de enfermedad y la tasa de respuesta objetiva, y aunque el estudio de Motzer et al., encuentra diferencias pequeñas respecto a la seguridad relacionadas a la fatiga y síndrome mano-pie en favor a pazopanib, estas diferencias bien podrían explicarse por las limitaciones metodológicas del ensayo clínico, por lo que permanecen por ser corroboradas en futuros estudios independientes. Además, existen diferencias respecto a efectos adversos en variables hematológicas (menor probabilidad de trombocitopenia en el grupo de pazopanib) y de la función hepática (menor probabilidad de hepatotoxicidad en \r\nel grupo de sunitinib) que no permiten justificar la recomendación de una droga sobre la otra. De hecho, la proporción de descontinuación del tratamiento por cualquier causa fue similar para pazopanib y sunitinib (88% en ambos grupos), aunque la descontinuación por efectos adversos fue ligeramente mayor para el grupo en pazopanib que en el sunitinib, principalmente por la descontinuación debida a la hepatotoxicidad (6% en el grupo de pazopanib, y 1% en el grupo de sunitinib). Actualmente, Essalud tiene disponible sunitinib aprobado para su uso fuera del petitorio mediante Dictamen Preliminar 004-SDEPFyOTS-DETS-IETSI-ESSALUD-2015 para primera línea de tratamiento en cáncer renal de células claras. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso de pazopanib como primera línea de tratamiento en cáncer renal de células claras.

Eficacia y seguridad de sunitinib en comparación con interferon Alfa 2a en pacientes con diagnósticos de carcinoma renal de células claras metastásico sin tratamiento previo / Efficacy and safety of sunitinib compared to interferon alfa 2a in patients with metastatic clear cell renal cell carcinoma without prior treatment

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del medicamento sunitinib respecto a su uso en pacientes con carcinoma renal de células claras metastásico que no hayan recibido tratamiento previo. Aspectos Generales: El carcinoma de células renames (CCR) representa el 2-3% de todas las neoplasias malignas a vinel mundial, siendo la séptima causa más común de cáncer en varones y la novena causa más común en mujeres. En perú, el 1.7% de todos los casos de cáncer reportados entre el 2006 y el 2011 fueron de origen renal. El carcinoma renal de células claras representa el 65-90% de todos los CCR (4-6) por lo que la mayor parte de estudios en CCR se hacen tomando como referencia a esta población. Tecnología Sanitaria de Interés: Sunitinib: Sunitinib es un inhibidor de un grupo de receptores de tirosina quinasa altamente relacionados. El sunitinib inhibe los receptores del VEGF y del factor de crecimiento derivado de plaquetas (PDFG, por sus siglas en inglés) en las células cancerígenas, células endoteliales vasculares y pericitos, inhibiendo la proliferación de células tumorales y el desarrollo de vasos sanguíneos tumorales. METODOLOGÍA: Estratégia de Búsqueda: Se realizó una búsqueda de la literatura con respecto al efecto de sunitinib sobre la sobrevida global, sobrevida libre de enfermedad, calidad de vida, perfil de eventos adversos y tasa de respuesta objetiva de pacientes con carcinoma renal de células claras metastásico sin tratamiento previo, en comparación con interferón alfa 2a, en las bases de datos MEDLINE. Se hizo una búsqueda adicional en www.clinicaltrials.gov, para poder identificar ensayos aun en elaboración o que no hayan sido publicados. Adicionalmente, se hizo una búsqueda dentro de la información generada por grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The National Guideline for Clearinghouse y The National Comprehensive Cancer Network (NCCN). RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de sunitinib como tratamiento de primera línea para pacientes con diagnóstico de CCR de células claras metastásico sin tratamiento previo. Se presente la evidencia identificada y correspondiente a guías de práctica clínica, revisiones sistemáticas y meta-análisis de los últimos 5 años; y ensayos clínicos aleatorizados de 2 anõs de antiguedad de acuerdo a los criterios de elegibilidad expuestos, excepto para el desenlace de calidad de vida en el que se amplió la búsqueda hasta el 2007 por no haber estudios recientes. CONCLUSIONES: De acuerdo a la revisión de las información existente, se concluye que el fármaco sunitinib administrado en dosis de 50 mg por día, en ciclos de 6 semanas (4 semanas de fármaco seguidas de 2 semanas de descanso) es una intervención recomendada sobre el INF-alfa 2a, para el tratamiento de primera línea de pacientes con cercinoma renal de células sin tratamiento previo, de pronóstico bueno o intermédio. Los estudios muestran un aumento consistente y significativo tanto de la sobrevida de enfermedad y la tasa de respuesta objetiva, así como e mismo perfil de eventos adversos. Sunitib mejora significativamente la calidad de vida relacionada a salud en estos pacientes, en comparación con INF-alfa, el cual se encuentra en el Petitorio Farmacoterapéutico de Essalud. El uso de sunitinib para pacientes de mal pronóstico no está recomendado. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, aprueba uso de sunitinib en cáncer renal de células claras metastásico sin tratamiento previo.

Current management and future directions in the treatment of advanced renal cell carcinoma-a latin american perspective: 10 years in review

ABSTRACT The worldwide incidence of kidney cancer is estimated at 337,860 new cases per year in the International Agency for Research on Cancer's GLOBOCAN 2012 update, with an estimated 143,369 deaths annually. Over the past 10 years, there have been significant advances in the treatment of advanced/metastatic renal cell carcinoma, including the development of targeted therapies. Currently recommended first-line treatments include sunitinib, temsirolimus, bevacizumab plus interferon, and pazopanib, or high-dose interleukin-2 or sorafenib for selected patients. Recommended second-line treatments include all of the above agents, as well as everolimus and axitinib. Unfortunately, combination therapies have generally resulted in increased toxicity and little improvement in efficacy. Recent studies focused on identification of predictive biomarkers for responses to specific targeted therapies and have not been successful to date. Despite recent advances in targeted treatment for metastatic renal cell carcinoma, important questions regarding biomarkers of efficacy, and optimal combination and sequencing of agents remain to be answered. This paper reviews literature concerned with first-and second-line treatment of metastatic renal cell carcinoma and will discuss key issues in Latin America.

Aortic dissection during antiangiogenic therapy with sunitinib. A case report / Dissecção de aorta em terapia anti-angiogênica com sunitinibe. Um relato de caso

CONTEXT: Sunitinib is an antiangiogenic drug that has been approved for treating metastatic renal cancer. Its action as a tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) and other angiogenesis receptors may lead to adverse effects such as hypertension and heart failure. However, reports in the literature on an association between sunitinib therapy and acute aortic dissection are rare. CASE REPORT: We report the case of a 68-year-old man with metastatic renal carcinoma who developed acute aortic dissection during sunitinib therapy. He had no history of hypertension or any other risk factor for aortic dissection. After aortic dissection had been diagnosed, sunitinib was withdrawn and an aortic endoprosthesis was placed. Afterwards, the patient was treated clinically with antihypertensive drugs and new therapy for renal cancer consisting of temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Hypertension is a common event when antiangiogenic drugs are used in oncology. However, knowledge of other severe cardiovascular events that may occur in these patients, such as acute aortic dissection, is important. Adequate control over arterial pressure and frequent monitoring of patients during the first days of antiangiogenic therapy is essential for early diagnosis of possible adverse events. .

CONTEXTO: Sunitinibe é uma droga antiangiogênica aprovada para tratamento de câncer renal metastático. Sua ação como inibidor de tirosina quinase de receptores de fatores de crescimento do endotélio vascular (VEGFR) e de outros receptores de angiogênese pode levar a eventos adversos como hipertensão e insuficiência cardíaca. No entanto, é escassa na literatura a associação da terapia com sunitinibe e dissecção aguda de aorta. RELATO DE CASO: Relatamos o caso de um paciente do sexo masculino de 68 anos com câncer renal metastático que desenvolveu dissecção aguda de aorta durante tratamento com sunitinibe. O paciente não tinha histórico prévio de hipertensão nem outro fator de risco para dissecção de aorta. Após diagnóstico da dissecção de aorta, a droga foi suspensa e o paciente foi submetido à colocação de endoprótese na aorta, evoluindo posteriormente com controle clínico da pressão arterial e nova terapia para câncer renal com tensirolimo, um inibidor da via proteína alvo da rapamicina em mamíferos (mTOR). CONCLUSÕES: A hipertensão é um evento comum com uso de drogas antiangiogênicas na oncologia. No entanto, é importante o conhecimento de outros eventos cardiovasculares graves, como dissecção aguda de aorta, que podem ocorrer nesses pacientes. Controle adequado da pressão arterial e monitorização frequente dos pacientes nos primeiros dias de terapia antiangiogênica são essenciais para diagnóstico precoce de possíveis eventos graves. .

Interferon treatment for Japanese patients with favorable-risk metastatic renal cell carcinoma in the era of targeted therapy

PURPOSE: Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy. MATERIALS AND METHODS: From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites. CONCLUSIONS: IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.

Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma patients

Purpose To assess the activity, safety and treatment patterns of sunitinib in patients with poor-risk metastatic renal cell carcinoma (mRCC). Materials and Methods We retrospectively reviewed the charts of poor risk patients treated with sunitinib from October 2006 to July 2013 who met the eligibility criteria. The primary endpoint was overall survival (OS). Tumor radiological response was measured according to RECIST 1.1 and adverse events (AEs) were assessed through standard criteria. Results Median OS was 8.16 months (95% CI, 5.73-10.59). Of the 53 patients included in this analysis, 9 (17.0%) achieved partial response, 12 (22.6%) had stable disease. Median treatment duration was 3.30 months (95% CI: 1.96-4.63) and 26.4% of patients discontinued treatment due to toxicity. Grade 3 or higher AEs occurred in 39.6% of patients, the most common being fatigue (15.1%), neutropenia (9.5%), nausea, vomiting and diarrhea (7.5% each). Discussion Sunitinib may benefit some unselected poor-risk patients, although the rates of AEs and drug discontinuation suggest a need for careful patient monitoring. .

Sorafenib in renal cell carcinoma

Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.

Systematic review and meta-analysis of target terapies for the treatment of metastatic renal cancer

Objectives At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). Materials and Methods SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). Results In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. Conclusions: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments. .

Sunitinib in metastatic renal cell carcimoma: A single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine‑kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty‑nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose‑modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression‑free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand–foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow‑up is essential for optimum therapy.

A Case of Pneumatosis Intestinalis Associated with Sunitinib Treatment for Renal Cell Carcinoma / 대한소화기학회지

Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.