RESUMEN
BRAF V600E mutations are associated with 8-10% of metastatic colorectal cancers (mCRC) and carry a poor prognosis with limited therapeutic options. In contrast to metastatic melanoma, BRAF inhibition alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitors has shown little utility in the treatment of BRAF V600E-mutant mCRC. This is secondary to upstream activation of the epidermal growth factor receptor (EGFR) pathway and other escape mechanisms. Combining RAF and MEK inhibitors with inhibition of the EGFR pathway through an anti-EGFR receptor antibody (cetuximab) led to the BEACON clinical trial (binimetinib, encorafenib and cetuximab). Trial patients had undergone at least one prior line of chemotherapy. The trial met all its endpoints and is now included in NCCN (National Comprehensive Cancer Network) guidelines. Herein we provide updates in treatment options for patients with BRAF V600E-mutant mCRC, focusing on the practice-changing BEACON-triplet regimen, the first chemotherapy-free combination regimen for mCRC. This combination is being explored frontline in the ANCHOR clinical trial.
Asunto(s)
Bencimidazoles/uso terapéutico , Carbamatos/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Quimioterapia Combinada , Humanos , Mutación , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Telotristat ethyl (Xermelo), developed by Lexicon Pharmaceuticals, is an oral tryptophan hydroxylase inhibitor blocking peripheral conversion of tryptophan to serotonin (5-hydroxytryptamine [5-HT]). It was approved by the U.S. Food and Drug Administration (FDA) in February 2017 and by the European Commission in September 2017 for patients with carcinoid syndrome in whom diarrhea is not adequately controlled by somatostatin analogues (SSAs). Diarrhea, secondary to the release of serotonin, is the predominant gastrointestinal symptom in patients with carcinoid syndrome and has a significant impact on patients' quality of life. Telotristat is not meant for all patients with diarrhea and carcinoid syndrome. Prescribing of telotristat for patients with diarrhea refractory to SSAs requires careful consideration and an approach that involves identifying and ruling out other common causes of diarrhea in patients with carcinoid syndrome. Delineating the timing of diarrhea and whether it occurs in patients with stable disease versus cancer progression can help identify the right drug candidates for therapy.
Asunto(s)
Diarrea/tratamiento farmacológico , Síndrome Carcinoide Maligno/tratamiento farmacológico , Fenilalanina/análogos & derivados , Pirimidinas/uso terapéutico , Somatostatina/análogos & derivados , Ensayos Clínicos como Asunto , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Fenilalanina/efectos adversos , Fenilalanina/farmacología , Fenilalanina/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/farmacologíaRESUMEN
INTRODUCTION: Osteoporosis-related bone fractures are a significant public health problem. The aim of this study was to determine the prevalence of osteoporosis among Pakistani women and identify modifiable risk factors. METHODS: A cross-sectional study was conducted in an obstetrics / gynaecology setting during March-April 2007 in Quetta, Pakistan. A total of 334 women older than 20 years of age underwent quantitative ultrasonography and were interviewed to find out the risk factors for osteoporosis. Bone mineral density was assessed by the speed of sound using a quantitative ultrasound device. The sociodemographic characteristics of normal, osteopenic and osteoporotic women were compared using the chi-square test for categorical variables and ANOVA for continuous variables. Binary logistic regression was used to determine the independent predictors of being osteopenic or osteoporotic. RESULTS: 146 (43.7 percent) women were reported to be normal, 145 (43.4 percent) were osteopenic and 43 (12.9 percent) were osteoporotic. The mean age and standard deviation of the participants were 36.7 years +/- 13.0 years, with a body mass index (BMI) of 25.81 (standard deviation 5.10) kg per square metre. In the univariate analysis, factors that were associated with osteoporosis / osteopenia included age, parity, BMI, smoking (pack years), consumption of calcium-rich food/week, personal and family history of osteoporosis, education and socioeconomic status (p-value is less than 0.05). Using binary logistic regression with osteoporosis / osteopenia as an outcome compared to normal individuals, BMI, smoking pack years, a family history of osteoporosis / fracture and house ownership were found to be independent predictors of the outcome. CONCLUSION: The prevalence of osteoporosis and osteopenia is high, especially among young Pakistani women, and is associated with modifiable risk factors.
Asunto(s)
Osteoporosis/diagnóstico por imagen , Adulto , Análisis de Varianza , Densidad Ósea , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Humanos , Entrevistas como Asunto , Modelos Logísticos , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/etiología , Osteoporosis/prevención & control , Pakistán/epidemiología , Prevalencia , Factores de Riesgo , UltrasonografíaRESUMEN
BACKGROUND: Epilepsy is a common but widely misunderstood illness. Consequently, epileptics suffer from considerable stigmatization in society. Since no studies have detailed the misperceptions about epilepsy in our community, it is not possible to provide focused intervention aimed at eliminating this prejudice. PURPOSE: To assess the knowledge and attitude regarding epilepsy in an adult population of a Karachi slum area. METHODS: A face-to-face interview was conducted on 487 consenting adult non-epileptics (305 males; 182 females) who were conveniently sampled. Chi-square test was employed to calculate the variability in knowledge and attitude with demographic and other variables. RESULTS: In all, 12.5% had never heard about epilepsy. Among the rest, 66.7% identified epilepsy as being non-infectious, while 28.2% were unaware of any treatment available for it. Among the other 71.8%, 62.7% were aware of the existence of anti-epileptic drugs. Religious/spiritual treatment was chosen as the most effective treatment by 33.1%. Males were more likely to identify epilepsy as being non-infectious (p=0.02). Nearly 18% of the respondents would not object to their child marrying an epileptic, 69.5% did not want to socially isolate the epileptics, 83.1% said epileptics could receive academic education, 85.6% said they could perform activities of daily life and 62.4% said they could become useful members of the society. Those who considered epilepsy to be infectious were more likely to carry negative attitudes towards epilepsy (p<0.01 with four attitudes). CONCLUSIONS: Considerable gaps exist in the community's knowledge about epilepsy. Some of these may explain the prevalence of negative attitudes towards this ailment.