Sunitinib induced resistance of endothelial cells by up-regulating P-glycoprotein and PI3K/Akt pathway

Abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling.

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.

Actualización de medicamentos asociados a necrosis avascular de los maxilares: perspectiva y revisión de literatura / Update of medications associated with avascular necrosis of the jaws: a perspective and literature review

La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)

Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (AU)

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.

Custo-efetividade do pazopanibe comparado ao sunitinibe para câncer renal metastático na perspectiva de um hospital do Sistema Único de Saúde / Cost-effectiveness between pazopanib and sunitinib for metastatic renal cancer from the perspective of the Brazilian Unified National Health System / Costo-efectividad entre el pazopanib y el sunitinib para el cáncer renal metastásico desde la perspectiva del Sistema Único de Salud

Resumo: O câncer renal é a 13ª neoplasia mais frequente no mundo. Entre 2012 e 2016, representou 1,48% das mortes por câncer no Brasil. A terapia de escolha para o tratamento de câncer renal metastático são os inibidores de tirosina quinase (ITK), sunitinibe e pazopanibe. Este artigo avalia o custo-efetividade do pazopanibe comparado ao sunitinibe no tratamento de câncer renal metastático. Foi realizada uma análise de custo-efetividade sob a perspectiva de um hospital federal do Sistema Único de Saúde. No modelo de árvore de decisão foram aplicados os desfechos de efetividade e segurança dos ITK. Os dados clínicos foram extraídos de prontuários e os custos diretos consultados em fontes oficiais do Ministério da Saúde. O custo de 10 meses de tratamento, englobando o valor dos ITK, procedimentos e manejo de eventos adversos, foi de R$ 98.677,19 para o pazopanibe e R$ 155.227,11 para o sunitinibe. Os medicamentos apresentaram efetividade estatisticamente equivalente e diferença estatisticamente significativa para o desfecho de segurança, no qual o pazopanibe obteve o melhor resultado. O pazopanibe, nesse contexto, é a tecnologia dominante quando os custos de tratamento são associados aos de manejo de eventos adversos.

Abstract: Renal cancer is the 13th most frequent neoplasm in the world. From 2010 to 2014, renal cancer accounted for 1.43% of cancer deaths in Brazil. The treatment of choice for metastatic renal cancer is tyrosine kinase inhibitors (TKI) sunitinib and pazopanib. This article assesses cost-effectiveness between pazopanib and sunitinib in the treatment of metastatic renal cancer. A cost-effectiveness study was performed from the perspective of a federal hospital under the Brazilian Unified National Health System (SUS). TKI effectiveness and safety outcomes were applied to the decision tree model. Clinical data were extracted from patient charts, and direct costs were consulted from official Ministry of Health sources. The cost of 10 months of treatment, including the costs of the TKI, procedures and management of adverse events, was BRL 98,677.19 for pazopanib and BRL 155,227.11 for sunitinib. The drugs displayed statistically equivalent effectiveness and statistically different safety outcomes, with pazopanib displaying better results. In this setting, pazopanib is the dominant technology when the treatment costs are analyzed together with the costs of managing adverse events.

Resumen: El cáncer renal es la 13ª neoplasia más frecuente en el mundo. Entre 2010 y 2014, representó un 1,43% de las muertes por cáncer en Brasil. La terapia de elección para el tratamiento de cáncer renal metastásico son los inhibidores de tirosina quinasa (ITK), sunitinib y pazopanib. Este artículo evalúa el costo-efectividad entre pazopanib y sunitinib en el tratamiento de cáncer renal metastásico. Se realizó un análisis de costo-efectividad desde la perspectiva de un hospital federal del Sistema Único de Salud. En el modelo de árbol de decisión se aplicaron los desenlaces de efectividad y seguridad de los ITK. Los datos clínicos se extrajeron de registros médicos, y los costos directos consultados en fuentes oficiales del Ministerio de Salud. El costo de 10 meses de tratamiento, englobando el valor de los ITK, procedimientos y gestión de eventos adversos, fue de BRL 98.677,19 con el pazopanib y BRL 155.227,11 con el sunitinib. Los medicamentos presentaron efectividad estadísticamente equivalente y diferencia estadísticamente significativa para el desenlace de seguridad, en el que el pazopanib obtuvo el mejor resultado. El pazopanib, en este contexto, es la tecnología dominante cuando los costes de tratamiento están asociados a los de la gestión de eventos adversos.

Tumor renal benigno versus carcinoma renal: reporte de caso y revisión de la literatura / Benign Kidney Tumor versus Renal Carcinoma: Case Report and Literature Review

Introducción El cáncer renal representa 2,4% de los casos diagnosticados de cáncer en la población general, es más común en hombres que en mujeres, y se presenta con más frecuencia entre la 6ta y la 8ta décadas de vida. Se estima que el 16% de los pacientes se diagnostican como enfermedad metastásica. Objetivo Se presenta el caso de un paciente cuyo diagnóstico de carcinoma renal se confundió inicialmente con un tumor benigno. Métodos A un hombre de 56 años de edad se le realizó hace 3 años ese diagnóstico en un estadio avanzado de la enfermedad, a pesar del hallazgo incidental de una masa, que se consideró benigna durante 5 años. Resultados Al momento del diagnóstico de carcinoma de células claras, el tumor era Estadio IV, con metástasis a pulmón. Recibió primera línea de tratamiento con sunitinib, pero fue suspendido por toxicidad; segunda línea con pazopanib durante 1 año, después presentó progresión de la enfermedad, por lo cual se cambió a tratamiento con axitinib con respuesta parcial, sin embargo, se suspendió por toxicidad cardiaca, entre otras. Al momento el paciente ha recibido 5 ciclos de bevacizumab con adecuada tolerancia. Conclusiones Es necesario resaltar la indicación de diagnóstico adecuado y manejo quirúrgico en masas renales sospechosas.

Introduction Kidney cancer represents 2.4% of diagnosed cases of cancer in the general population; it is more common in men than in women, and occurs more frequently between the 6th and 8th decades of life. It is estimated that 16% of patients are diagnosed as metastatic disease. Objective To report the case of a male patient whose diagnosis of renal carcinoma was initially misdiagnosed as a benign tumor. Methods We present a 56-year-old male diagnosed three years back with malignancy at an advanced stage of the disease, despite the incidental finding of a tumor that for 5 years was considered benign. Results At the time of diagnosis of clear cell carcinoma, the tumor was Stage IV, with lung metastasis. He received first line treatment with sunitinib, which was discontinued due to toxicity. Subsequently, a second line with pazotinib for 1 year, then presented progression of the disease, so treatment was changed to axitinib with partial response., It was discontinued, however, due to cardiac toxicity, among others. At the time of writing, the patient has received 5 cycles of bevacizumab with adequate tolerance. Conclusions It is necessary to highlight the need for adequate diagnosis and surgical management in suspicious renal masses.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules / Avaliação das alterações retinais no coelho após injeção intravítrea de sunitinib encapsulado em nanoparticulas lípidas sólidas e nanocapsulas polímeros

ABSTRACT Purpose: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. Methods: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. Results: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. Conclusions: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

RESUMO Objetivos: O presente estudo teve por objetivo avaliar a segurança da injeção intravítrea de 0,1 ml de sunitinibe em duas concentrações (1 mg/ml e 10 mg/ml), 0,1 ml de dispersão contendo nanopartículas lipídicas sólidas sem droga e 0,1 ml de dispersão contendo nanocápsulas poliméricas livre de drogas analisando os possíveis efeitos tóxicos à retina de coelhos albinos detectados pela eletrofisiologia e histologia por microscopia óptica. Métodos: Um estudo controlado experimental foi rea­lizado com 20 olhos de coelhos albinos. Foram realizadas injeções intravítrea de duas concentrações diferentes de suniti­nibe, uma dispersão contendo nanopartículas lipídicas sólidas e uma dispersão contendo nanocápsulas. O olho contralateral não recebeu tratamento e foi utilizado como controle. Resultados: Não foram observadas alterações eletrorretinográficas nos grupos do sunitinibe (1 mg/ml e 10 mg/ml) e no grupo das nanopartículas lipídicas sólidas. No grupo das nanocápsulas, houve alterações significativas tanto na morfologia, quanto na amplitude e tempo das ondas do eletrorretinograma. Ao estudo histológico, somente o grupo das nanocápsulas apresentou al­terações degenerativas (núcleos tumefeitos) com acentuado edema e formação de vacúolos citoplasmáticos, sugerindo toxidade retiniana. Conclusões: As injeções intravítreas de sunitinibe e nanopartículas lipídicas sólidas não foram tóxicas para a retina. No entanto, nanocápsulas mostraram ser tóxicas para a retina. Sendo assim, a possibilidade de poder combinar o potencial de uma droga que possui a capacidade de inibir duas importantes vias da angiogênese, às vantagens de liberação controlada das nanopartículas lipídicas sólidas, pode ser um importante recurso terapêutico para doenças vasoproliferativas oculares.

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor

SUMMARY Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.

Fosfatasa alcalina ósea sérica elevada no mediada por metástasis en un paciente con cáncer renal / Elevated bone alkaline phosphatase not mediated by metastasis in a patient with renal cancer

Presentamos un paciente de 63 años con cáncer renal y aumento de fosfatasa alcalina sérica de tipo óseo de acuerdo con su reactividad con anticuerpos monoclonales específicos. Se descartaron las causas conocidas de aumento de la isoenzima, incluyendo metástasis óseas. Los niveles enzimáticos cayeron abruptamente con la remoción del tumor, por lo que consideramos a este último como su origen. Diversas isoenzimas de fosfatasa alcalina pueden ser producidas y secretadas por tumores como manifestación paraneoplásica. El conocimiento de esto puede, en ocasiones, orientarnos hacia la presencia de una neoplasia oculta. Además, los cambios en los niveles séricos de esas isoenzimas pueden ser indicadores de respuesta al tratamiento o de recidiva tumoral. (AU)

A 63-year old man was seen in the outpatient clinic because of renal cancer and elevation in bone alkaline phosphatase measured by monoclonal antibodies assay. Known causes of bone isoenzyme augmentation, including bone metastases, were ruled out. The tumoral origin of the isoenzyme was diagnosed because after removal of the tumor the enzymatic levels fell sharply. Several alkaline phosphatase isoenzymes can be produced and secreted by tumors as a paraneoplasic manifestation and their elevation could be a manifestation of an occult neoplasia. Furthermore the monitoring of their blood levels can be useful means of treatment response and a tool to monitoring recurrence if a sharp decrease after removal of the tumor is observed. (AU)

Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature

SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.

Estudio de variables y perfil inmunohistoquímico en pacientes con carcinoma de células renales / Study of variables and immunohistochemical profile in patients with renal cell carcinoma

En el 40% de los casos de carcinoma de células renales (CCR) se desarrollan metástasis después de la nefrectomía. En estadios avanzados la sobrevida es baja y los pacientes no siempre responden a la terapia actual con inhibidores de tirosinas quinasas (TKI). Con el propósito de encontrar nuevas dianas terapéuticas estudiamos 20 casos de CCR. Se observó una mayor frecuencia en hombres (60%) y en cuanto al grupo etario, un alto porcentaje de los estudiados fueron adultos jóvenes (40%). Solamente los pacientes en estadio IV recibieron tratamiento con TKI (Sunitinib). Por inmunohistoquímica se observó que ErbB-2 de membrana se expresó en el 40% de los CCR Células Claras. Se plantea la hipótesis que, este oncogén podría servir como diana terapéutica en nuestra población

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.

Estudio de tiempo de progresión y sobrevida global en pacientes con cáncer renal de células claras metastásico tratados con Sunitinib en el servicio de Oncología del Hospital Carlos Andrade Marín en el período comprendido entre enero de 2010 a diciembre de 2012 / Progression and global survival times study in patients with clear-cell terminal kidney cancer treated with Sunitinib in the Carlos Andrade Marin Hospital Oncolgy department during the January 2010 ­ December 2012 period

Introducción: el carcinoma renal de células claras (CRCC) es el más común de los cánceres del riñón, al tiempo del diagnóstico un 30% de pacientes presenta metástasis y un 40% se encuentra en recurrencia de la enfermedad. Es altamente resistente al tratamiento de quimioterapia y se ha evidenciado pobres respuestas con las interleuquinas e interferón antes utilizados, por lo que actualmente la terapia blanco con inhibidores de la tirosina quinasa son utilizados. Este estudio tiene como objetivo establecer la sobrevida global y el tiempo de progresión en pacientes con CRCC metastásico tratados con Sunitinib. Materiales y métodos: estudio clínico de cohorte analítico retrospectivo, con análisis de supervivencia mediante la técnica de Kaplan Meier. Se revisan las historias clínicas de 42 pacientes con diagnóstico de cáncer renal de células claras (CRCC) metastásico tratados con el inhibidor de tirosin quinasa Sunitinib en el servicio de Oncología del Hospital Carlos Andrade Marín durante el período comprendido entre el primero de enero de 2010 y 31 de diciembre de 2012 para obtener variables clínicas y realizar análisis de supervivencia. Resultados: 42 pacientes analizados con cáncer renal metastásico de células claras, 22 de ellos recibieron tratamiento con Sunitinib y 20 no recibieron este tratamiento, encontrando que la mediana de sobrevida para el grupo de pacientes tratados con Sunitinib fue de 16 meses versus 4,5 meses para los pacientes que no recibieron. La mediana del tiempo de progresión en el grupo de Sunitinib fue de 6 meses. Conclusiones: los resultados del análisis de tiempo de progresión en los pacientes tratados con Sunitinib fue similar a los estudios de referencia y guías de manejo oncológicos internacionales. En términos de sobrevida se obtuvo un resultado favorable sin embargo, los resultados aún no son concluyentes.

Introduction: the clear cell renal cell carcinoma (CRCC) is the most common cancer of the kidney, at the time of diagnosis 30% of patients have metastases and 40% are in disease recurrence. It is highly resistant to chemotherapy and poor responses were evidenced with the interleukins and interferon before use, so that the current target therapy with tyrosine kinase inhibitors were used. The objective of this study is to determine the survival and time to progression in patients with metastatic CRCC treated with Sunitinib. Materials and methods: retrospective study by Kaplan Meier technique, using the statistical package Epi Info 3.5, in patients with metastatic CRCC evaluated in the oncology department in the period between january 2010 and december 2012. Results: 42 patients with CRCC clear cell were analyzed, 22 of them were treated with Sunitinib and 20 did not receive this treatment. Findings show that the median survival for the group of patients treated with Sunitinib was 16 months versus 4.5 months for patients who did not. The median time to progression in the Sunitinib was 6 months. Conclusions: the results of the analysis of time of progression in patients treated with Sunitinib were similar at baseline and according to international oncology management guidelines. Favorable results were obtained in terms of survival; however results still are inconclusive.