ABSTRACT
OBJECTIVE: Over the last decade, significant advances have been made in the development of therapies for patients with metastatic castration-resistant prostate cancer. Abiraterone and enzalutamide were approved as treatments based on data supporting improved overall survival compared to placebo. Radium-223 became the first approved radiopharmaceutical which decreased skeletal-related events, palliated pain, and showed improved overall survival in symptomatic patients with castration-resistant prostate cancer and bone metastasis only. MATERIALS AND METHODS: We present the case of an eighty-two year old man with metastatic castration-resistant prostate cancer who was treated with sequential therapy (abiraterone - enzalutamide - radium 223). The sequencing and treatment used for our patient was viable because of his clinical characteristics, which have allowed for longer survival time with an acceptable quality of life. These actions must be agreed on by the Multidisciplinary Tumour Board, in order to optimize the use of available courses of treatment. RESULTS: The treatment of these patients is changing rapidly, but many questions remain regarding the optimal sequencing of the available drugs. Sequential or concomitant use of the next generation hormonal agents - abiraterone and enzalutamide - cannot currently be recommended. Data regarding the safety of concomitant abiraterone, enzalutamide or denosumab with radium-223 is reassuring and timely. However, we cannot advocate the general use of combined radium-223 therapy at this time, irrespective of prior therapy. CONCLUSION: A better understanding of active mechanisms, the genetic characteristics of each metastatic castration-resistant prostate cancer and the development of new prognostic and predictive biomarkers will help determine sequencing or different combination treatments for each individual patient.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prostatic Neoplasms/therapy , Radium/therapeutic use , Abiraterone Acetate/administration & dosage , Aged, 80 and over , Benzamides , Biomarkers, Tumor , Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Combined Modality Therapy , Humans , Male , Neoplasm Metastasis , Neoplasm Staging , Nitriles , Phenylthiohydantoin/administration & dosage , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms/diagnosis , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
The objective of the study was to quantify annual and seasonal differences in the chemical composition, in vitro gas production, in situ degradability and ruminal fermentation of grazing steers' diets. Diet samples were collected with four esophageal cannulated steers (350±3 kg BW); and four ruminally cannulated heifers (342±1.5 kg BW) were used to study the dry matter degradation and fermentation in rumen. Data were analyzed with repeated measurements split plot design. The crude protein, in vitro dry matter digestibility and metabolizable energy were higher during the first year of trial and in the summer (p<0.01). The values of calcium, phosphorus, magnesium, zinc and copper were higher in summer (p<0.05). The gas produced by the soluble and insoluble fractions, as well as the constant rate of gas production were greater in summer and fall (p<0.01). The ammonia nitrogen (NH3N) and total volatile fatty acids concentrations in rumen, the soluble and degradable fractions, the constant rate of degradation and the effective degradability of DM and NDF were affected by year (p<0.05) and season (p<0.01). Our study provides new and useful knowledge for the formulation of protein, energetic and mineral supplements that grazing cattle need to improve their productive and reproductive performance.
