Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

Heparinas de bajo peso molecular en la profilaxis de episodios tromboembólicos en pacientes con cáncer portadores de catéter venoso central / Role of low molecular weight heparins in prophylaxis of thromboembolic events on oncological patients with indwelling central venous catheter

Fundamento y objetivo: Este estudio pretende analizar la incidencia de trombosis de extremidades superiores y de embolia pulmonar en pacientes oncológicos portadores de catéter venoso central, así como valorar si las heparinas de bajo peso molecular (HBPM) podrían ser útiles en prevenir este tipo de episodios. Pacientes y método: Pacientes oncológicos portadores de catéter tipo porth a cath se trataron con bemiparina o no de forma no aleatorizada; se realizó seguimiento clínico y radiológico mediante flebografía el día 1 y ecografía Doppler los días 1, 45 y 90 tras la implantación. Se determinó la incidencia de trombosis en pacientes con o sin tratamiento con bemiparina sódica (3.500 U/día) y su relación con posibles factores de riesgo. Resultados: Se encontraron 19 episodios trombóticos en 148 pacientes elegibles: el 5,41% de trombosis venosa profunda de extremidad superior sintomática y el 2,03% asintomática; un caso de embolia pulmonar (0,68%); el 2,70% de disfunción del catéter, y el 2,03% de trombosis de extremidades inferiores. Hubo mayor porcentaje de episodios trombóticos en el grupo de tratamiento con HBPM (15,5%) que en el grupo sin profilaxis (9,4%); la diferencia no fue significativa (p=0,272). Los únicos factores de riesgo significativos fueron el tiempo de protrombina, la hipertensión arterial y el sobrepeso. Conclusiones: La colocación de catéteres venosos centrales es una técnica de gran utilidad, con bajo porcentaje de complicaciones trombóticas clínicamente manifiestas. La bemiparina sódica no presenta una relación favorable para disminuir el riesgo de trombosis en estos enfermos (AU)

Background and objective: Our study was designed to assess the incidence of thrombosis in the upper limbs and of pulmonary embolism in oncological patients with indwelling central venous catheters, and to evaluate, also, the potential role of LMWH to prevent these events. Patients and methods: Oncological patients undergoing placement of a central venous acccess (port-a-cath type) were treated with or without bemiparin in a non-randomized fashion. Assessment included clinical and radiological follow-up. A phlebography on the first day and ecodoppler on days 1th, 45th and 90th were performed. Patients received or not prophylactic bemiparin (3500UI/day) in a non-randomized way. The incidence of thrombosis in both groups was assessed as well as its relation with some risk factors. Results: One hundred and forty eight patients were eligible; 19 thrombotic events were found. The incidence of symptomatic upper extremity thrombosis was 5.41%, asymptomatic thrombosis in 2.03% ; there was one case of pulmonary embolism ( 0,68%); catheter failure occurred in 2.70%; incidence of lower extremities deep venous thrombosis was 2.03%. There was a higher percentage of events in the group of patients treated with bemiparin than in the not treated individuals (9.4%), although the difference did not reach statistical significance (p=0.27). The only risk factors reaching statistical significance were the prothrombin time, high blood pressure and overweight. Conclusions: Central venous catheters are very useful in oncology. The procedure was related with a low percentage of thrombotic complications. Sodic bemiparin does not reduce the thrombotic risk in these patients (AU)

[Role of low molecular weight heparins in prophylaxis of thromboembolic events on oncological patients with indwelling central venous catheter]. / Heparinas de bajo peso molecular en la profilaxis de episodios tromboembólicos en pacientes con cáncer portadores de catéter venoso central.

BACKGROUND AND OBJECTIVE: Our study was designed to assess the incidence of thrombosis in the upper limbs and of pulmonary embolism in oncological patients with indwelling central venous catheters, and to evaluate, also, the potential role of LMWH to prevent these events. PATIENTS AND METHODS: Oncological patients undergoing placement of a central venous acccess (port-a-cath type) were treated with or without bemiparin in a non-randomized fashion. Assessment included clinical and radiological follow-up. A phlebography on the first day and ecodoppler on days 1th, 45th and 90th were performed. Patients received or not prophylactic bemiparin (3500UI/day) in a non-randomized way. The incidence of thrombosis in both groups was assessed as well as its relation with some risk factors. RESULTS: One hundred and forty eight patients were eligible; 19 thrombotic events were found. The incidence of symptomatic upper extremity thrombosis was 5.41%, asymptomatic thrombosis in 2.03% ; there was one case of pulmonary embolism ( 0,68%); catheter failure occurred in 2.70%; incidence of lower extremities deep venous thrombosis was 2.03%. There was a higher percentage of events in the group of patients treated with bemiparin than in the not treated individuals (9.4%), although the difference did not reach statistical significance (p=0.27). The only risk factors reaching statistical significance were the prothrombin time, high blood pressure and overweight. CONCLUSIONS: Central venous catheters are very useful in oncology. The procedure was related with a low percentage of thrombotic complications. Sodic bemiparin does not reduce the thrombotic risk in these patients.

[Novel therapeutic targets in metastatic renal cell carcinoma. Results of the treatment with single-agent bevacizumab in a single institution]. / Nuevas dianas terapéuticas para el carcinoma de células renales metastásico. Resultados del tratamiento con bevacizumab en monoterapia en un único centro hospitalario.

AIM: Along the past decade a number of new agents have been developed showing promising results in the treatment of metastatic renal cell carcinoma. We describe our experience with the use of bevacizumab in monotherapy in the Urology and Medical Oncology departments of our institution. MATERIAL AND METHODS: A consecutive series of patients treated with Bevacizumab 10 mg/Kg every 14 days between January 2006 and January 2008 has been assessed. Data concerning the type of surgery, histological subtype, tumor stage, Motzer's risk group, metastatic sites number of bevacizumab courses given, time to progression and overall survival were collected. RESULTS: 25 patients (16 male, 9 female) were analyzed. Median age was 59 years. Nineteen of them (75%) had prior surgery: radical nephrectomy 14, cytoreductive 4 y tumorectomy 1). Clear cell carcinoma was the most frequent subtype (22 patients). According to Motzer's prognostic index 14 had good prognosis, 8 intermediate and 3 poor prognosis. Median time to progression was 19 weeks. Overall median survival since metastatic disease was diagnosed 8,7 months. CONCLUSIONS: Bevacizumab offers, as single agent, modest activity in the metastatic renal cell carcinoma. The recently labeled use in combination with interferon as well as the newer targeted agents will improve the results of the treatment of this disease in the next future.

Nuevas dianas terapéuticas para el carcinoma de células renales metastásico. Resultados del tratamiento con bevacizumab en monoterapia en un único centro hospitalario / Novel therapeutic targets in metastatic renal cell carcinoma. Results of the treatment with single-agent bevacizumab in a single institution

Objetivos: En la última década se están desarrollando multitud de nuevas moléculas que ofrecen resultados esperanzadores para el tratamiento del CCR metastásico. Este estudio describe nuestra experiencia en 25 pacientes tratados con bevacizumab en monoterapia. Material y métodos: Se analizan los resultados obtenidos en 25 pacientes con CCR metastásico tratados con Bevacizumab (10 mg/Kg quincenal) entre enero del 2006 y enero del 2008. Se recogieron datos acerca del tipo de cirugía practicada, tipo histológico, estadio tumoral, grupo de riesgo de Motzer, localizaciones metastásicas, número de ciclos administrados, tiempo hasta la progresión y supervivencia global. Resultados: Se analizaron 25 pacientes (16 varones y 9 mujeres), con una mediana de edad de 59 años. Más de la mitad de ellos (19) se había sometido a algún tipo de intervención quirúrgica (14 nefrectomía radical, 4 citorreductora y 1 tumorectomía). La mayor parte de los enfermos presentaban histología de células claras (22). 14 pacientes pertenecían al grupo de buen pronóstico de Motzer, 8 al grupo de pronóstico intermedio y 3 al de mal pronóstico. La mediana de tiempo hasta la progresión fue de 19 semanas, con una mediana de supervivencia global desde el inicio de tratamiento de 8,7 meses. Conclusiones: El bevacizumab en monoterapia ofrece unos resultados modestos para el tratamiento del CCR metastásico. Su reciente aprobación en combinación con Interferon, y la aparición progresiva de distintas dianas terapéuticas, permitirá optimizar los resultados en los próximos años (AU)

Aim: Along the past decade a number of new agents have been developed showing promising results in the treatment of metastatic renal cell carcinoma. We describe our experience with the use of bevacizumab in monotherapy in the Urology and Medical Oncology departments of our institution. Material and methods: A consecutive series of patients treated with Bevacizumab 10 mg/Kg every 14 days between January 2006 and January 2008 has been assessed. Data concerning the type of surgery, histological subtype, tumor stage, Motzer’s risk group, metastatic sites number of bevacizumab courses given, time to progression and overall survival were collected. Results: 25 patients (16 male, 9 female) were analyzed. Median age was 59 years. Nineteen of them (75%) had prior surgery: radical nephrectomy 14, cytoreductive 4 y tumorectomy 1). Clear cell carcinoma was the most frequent subtype (22 patients). According to Motzer’s prognostic index 14 had good prognosis, 8 intermediate and 3 poor prognosis. Median time to progression was 19 weeks. Overall median survival since metastatic disease was diagnosed 8,7 months. Conclusions: Bevacizumab offers, as single agent, modest activity in the metastatic renal cell carcinoma. The recently labeled use in combination with interferon as well as the newer targeted agents will improve the results of the treatment of this disease in the next future (AU)