Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment (AU)

Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept.

Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient's profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

[Lipid lowering treatment of severe hypertriglyceridemia with acute pancreatitis caused by everolimus in a patient with a neuroendocrine tumor]. / Tratamiento hipolipemiante de la pancreatitis aguda secundaria a hipertrigliceridemia severa por everolimus en un paciente con tumor neuroendocrino.

Everolimus is an mTOR inhibitor, approved as a treatment for cancer and as an immunosuppressant agent in solid organ transplantation; it frequently produces toxic metabolic effects, particularly of the most severe kind. Its use can cause hyperglycemia, hypercholesterolemia and hypertriglyceridemia; thus, metabolic values should be monitored regularly to prevent these adverse events. We present the case of a woman with an intestinal neuroendocrine tumor who developed two episodes of acute pancreatitis, secondary to severe hypertriglyceridemia caused by everolimus. After treatment with fibrates and omega-3, triglyceride levels returned to baseline, without developing new metabolic or digestive complications. Targeted levels of triglyceride for cancer patients treated with everolimus, should be below 500 or 300 mg/dL, depending on whether life expectancy is less or longer than one year, respectively.

Tratamiento hipolipemiante de la pancreatitis aguda secundaria a hipertrigliceridemia severa por everolimus en un paciente con tumor neuroendocrino / Lipid lowering treatment of severe hypertriglyceridemia with acute pancreatitis caused by everolimus in a patient with a neuroendocrine tumor

Everolimus es un inhibidor de mTOR, empleado en oncología y como inmunosupresor en el trasplante de órgano sólido. Sus efectos adversos a nivel metabólico son muy frecuentes, especialmente los más severos. Puede ocasionar hiperglucemia, hipercolesterolemia e hipertrigliceridemia, por lo que la monitorización de los parámetros metabólicos en las sucesivas visitas es vital para detectar e iniciar tratamientos que puedan prevenir las complicaciones. Se presenta el caso de una mujer con diagnóstico de tumor neuroendocrino intestinal que desarrolló dos pancreatitis agudas secundarias a hipertrigliceridemia severa por everolimus. Tras inicio de tratamiento con fibratos y omega-3, se normalizó la cifra de triglicéridos sin presentar nuevas complicaciones metabólicas ni digestivas secundarias al fármaco. La recomendación en pacientes con cáncer en tratamiento activo con everolimus es mantener los triglicéridos por debajo de 500 o 300 mg/dL, dependiendo de si la esperanza de vida es inferior o superior a un año, respectivamente

Everolimus is an mTOR inhibitor, approved as a treatment for cancer and as an immunosuppressant agent in solid organ transplantation; it frequently produces toxic metabolic effects, particularly of the most severe kind. Its use can cause hyperglycemia, hypercholesterolemia and hypertriglyceridemia; thus, metabolic values should be monitored regularly to prevent these adverse events. We present the case of a woman with an intestinal neuroendocrine tumor who developed two episodes of acute pancreatitis, secondary to severe hypertriglyceridemia caused by everolimus. After treatment with fibrates and omega-3, triglyceride levels returned to baseline, without developing new metabolic or digestive complications. Targeted levels of triglyceride for cancer patients treated with everolimus, should be below 500 or 300 mg/dL, depending on whether life expectancy is less or longer than one year, respectively

New clinical trials regulation in Spain: analysis of royal decree 1090/2015

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient’s safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as «low-intervention clinical trial». The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects’ safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research (AU)

No disponible

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Quality of Life assessment through the EORTC questionnaires of colorectal cancer patients in advanced disease stages

PURPOSE: The purpose of the present work is to evaluate Quality of Life in a group of colorectal cancer patients in advanced stages of their disease, along a standard chemotherapy treatment protocol, through the EORTC core questionnaire QLQ-C30 and the colorectal cancer module QLQ-CR38. These two questionnaires had previously been validated in our country. The present study has the novelty of its use during the chemotherapy treatment. MATERIALS AND METHODS: A consecutive sample of 44 colon o rectal cancer patients in stage IV, from an initial group of 46 patients who were addressed, have filled in the questionnaires, in three moments during their treatment process. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. RESULTS: The quality of life scores of patients who have followed the treatment have been >70 points (100) in most dimensions, and has shown similar to the clinical data. Changes of >20 points in the quality of life scores during the treatment process appear in areas related to toxicity, fatigue and insomnia. Quality of life has been stable or has had small changes (between 10 and 20 points) in most dimensions. CONCLUSIONS:Quality of Life in the present sample has been good in general. The treatment has been administered to patients who could tolerate it adequately (AU)

Quality of life assessment in Spanish lung cancer patients by the EORTC questionnaires

• Propósito: el objetivo de este trabajo es evaluar la calidad de vida de una muestra de pacientes con cáncerde pulmón durante el tratamiento.• Metodos: 170 pacientes con cáncer de pulmón, microcítico con enfermedad limitada y avanzada, y nomicrocítico estadíos III y IV. Los pacientes han contestado el cuestionario EORTC QLQ-C30 y el módulo depulmón EORTC-LC13 en tres momentos a lo largo del tratamiento y seguimiento. Se han recogido datos demográficosy clínicos. Se han comparado grupos formados en función del estadio y tratamiento, y se han estudiadolos cambios en la calidad de vida a lo largo del tiempo.• Resultados: las puntuaciones de calidad de vida de los pacientes que han recibido los protocolos propuestosson aceptables en las tres mediciones al igual que las puntuaciones de toxicidad. En la medición de líneabase hay limitaciones en las áreas de síntomas de la enfermedad y la calidad de vida global. Hay pocas diferenciasentre grupos organizados según tipos de tratamiento y estadio de la enfermedad. Las puntuaciones decalidad de vida son muy similares en las tres mediciones. Los tratamientos tienen un efecto específico en la segundamedición, que mejora en la tercera en algunas áreas de toxicidad, y en otras persiste.• Conclusiones: la calidad de vida de los pacientes que han recibido los protocolos completos es adecuada.Los pacientes que reciben los tratamientos pueden tolerarlos adecuadamente

• Purpose: To assess the quality of life of a sample of lung cancer patients during their treatment.• Material and methods: 170 patients with limited and advanced small-cell lung cancer (SCLC), andwith stages III and IV non-small cell lung cancer (NSCLC) were considered. Patients filled the EORTC QLQC30questionnaire, and the EORTC-LC13 lung module at three different times during the treatment andfollow-up. Demographic and clinical data were also recorded. We compared the groups according to the stageand treatment modality, and studied the changes of the quality of life throughout time.• Results: The quality of life scores of the patients under the given protocols: were acceptable in the threeconsidered measurements, as were also the toxicity scores. At the base line there are limitations in the areas ofsymptoms of disease and quality of life. Few differences were observed between the groups at different stagesand under the different treatment modalities. The quality of life scores were similar according to the threemeasurements. Treatment modality showed a specific effect in the second measurement, while in the third oneit improved in some toxicity areas and persisted in others.• Conclusions: The quality of life of the patients receiving the complete protocols was acceptable. Thepatients under treatment stood it adequately

Evaluación de la calidad de vida a largo plazo en pacientes con cáncer de mama en estadios iniciales mediante los cuestionarios de la EORTC / Evaluation through the EORTC questionnaires of long-term quality of life in patients with breast cancer in initial stages

Fundamento. El objetivo del presente trabajo es evaluar la calidad de vida de un grupo de pacientes con cáncer de mama tras un período de seguimiento largo. Métodos. Ciento cuatro pacientes con cáncer de mama en estadios iniciales, de un total de 125 que se habían contactado, han completado el cuestionario general QLQ-C30 y el módulo de mama QLQ-BR23 de la EORTC en 2001, 5 años después de su diagnóstico. Un subgrupo de 48 habían completado estos cuestionarios en 1996. Se han evaluado las puntuaciones de calidad de vida, las diferencias entre las mediciones de 2001 y 1996 y comparado grupos organizados según estadio, tipo de tratamiento y de cirugía. Resultados. Las puntuaciones de calidad de vida son adecuadas y similares en ambos períodos (1996 y 2001). Hay afectaciones en funcionamiento sexual y preocupación por el futuro. Las diferencias entre tipo de cirugía se centran en la imagen corporal. No hay diferencias significativas en los análisis por estadio o tipo de tratamiento. Conclusiones. Las puntuaciones de calidad de vida indican que la situación de estas pacientes es satisfactoria. Las diferencias en tipo de cirugía están en línea con la literatura (AU)

[Evaluation through the EORTC questionnaires of long-term quality of life in patients with breast cancer in initial stages]. / Evaluación de la calidad de vida a largo plazo en pacientes con cáncer de mama en estadios iniciales mediante los cuestionarios de la EORTC.

BASIS: The objective of the present work is to evaluate the quality of life of a group of patients with breast cancer after a long follow-up time. METHODS: 104 patients with breast cancer in initial stages, of a total of 125 to whom the questionnaire was sent, have completed the general questionnaire QLQ-C30 and the module of the breast QLQ-BR23 of the EORTC in 2001, five years after their diagnosis. A subgroup of 48 patients had completed these questionnaires in 1996. The scorings of quality of life and the differences among the measurements of 2001 and 1996 have been evaluated, and groups organized according to the stage, the type of treatment, and the surgery have been compared. RESULTS: The scorings of quality of life are appropriate and similar in both periods (1996 and 2001). There are alterations in the sexual function and concern over the future. The differences between the type of surgery focus on the corporal image. There are not significant differences in the analyses according to the stage or according to the type of treatment. CONCLUSIONS: The scorings of quality of life indicate that the situation of these patients is satisfactory. The differences in the type of surgery are similar to the ones observed in the literature.

Minerals content of Paraguayan yerba mate (Ilex paraguariensis, S.H.).

Minerals content (Fe, Ca, Mn, Mg, Na, K, Zn and Cu) of the leaves of Paraguayan yerba mate (Ilex paraguariensis, S.H.) as well as of commercial products has been determined by atomic absorption spectrophotometry. Considerable amounts of iron and calcium and remarkably high content of magnesium and potassium have been found both in the leaves and in the commercial products. Highly significant difference between the Fe content of the leaves and that of the commercial products has been found. Also, highly significant difference has been found between the Fe and Ca content of the higher quality-greater sale reputed commercial products and that of the lower quality-smaller sale reputed ones. Seasonal and soil linked variations are also presented. The nutritional and quality control significance of these findings for the MERCOSUR (Southern South America Economical Community) are discussed.