Potential Use of Custirsen to Treat Prostate Cancer.

Potential use of custirsen to treat prostate cancer.

Onco Targets Ther. 2013; 6: 785-97
Higano CS

Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy); cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents); and radium 223 (an alpha emitter). The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011) is a second-generation 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials. HubMed – drug

Drugs for solid cancer: the productivity crisis prompts a rethink.

Onco Targets Ther. 2013; 6: 767-77
Rösel D, Brábek J, Veselý P, Fernandes M

Despite remarkable progress in cancer-drug discovery, the delivery of novel, safe, and sustainably effective products to the clinic has stalled. Using Src as a model, we examine key steps in drug development. The preclinical evidence on the relationship between Src and solid cancer is in sharp contrast with the modest anticancer effect noted in conventional clinical trials. Here, we consider Src inhibitors as an example of a promising drug class directed to invasion and metastasis and identify roadblocks in translation. We question the assumption that a drug-induced tumor shrinkage in preclinical and clinical studies predicts a successful outcome. Our analysis indicates that the key areas requiring attention are related, and include preclinical models (in vitro and mouse models), meaningful clinical trial end points, and an appreciation of the role of metastasis in morbidity and mortality. Current regulations do not reflect the natural history of the disease, and may be unrelated to the key complications: local invasion, metastasis, and the development of resistance. Alignment of preclinical and clinical studies and regulations based on mechanistic trial end points and platforms may help in overcoming these roadblocks. Viewed kaleidoscopically, most elements necessary and sufficient for a novel translational paradigm are in place. HubMed – drug

Pattern of sudden death at Ladoke Akintola University of Technology Teaching Hospital, Osogbo, South West Nigeria.

Vasc Health Risk Manag. 2013; 9: 333-9
Akinwusi PO, Komolafe AO, Olayemi OO, Adeomi AA

The purpose of this study was to determine the etiology and epidemiologic characteristics of sudden death at Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, South West Nigeria.This was a retrospective descriptive study of all cases of natural unexpected death, either occurring out of hospital or less than 24 hours after admission to LAUTECH Teaching Hospital, over a nine-year period from January 2003 to December 2011. Data were generated from information in the case notes and autopsy reports for these cases.Sudden death accounted for 29 (4.0%) of 718 adult medical deaths and 1.0% of all adult medical admissions. Out-of-hospital deaths occurred in 72.4% of cases. The mean age of the patients was 46.8 ± 11.5 (range 25-74) years. The male to female ratio was 6.25:1. Cardiovascular disease were the most common cause of death (51.7%), followed by respiratory disease (20.7%), pulmonary thromboembolism (10.4%), central nervous system disease (13.8%), gastrointestinal disorders (13.8%), severe chemical/drug poisoning (13.8%), and combined cardiovascular and central nervous system disease (13.8%). Hypertension-related causes were responsible for 14/29 (48.3%) of the sudden deaths. Hypertensive heart disease accounted for 86.7% of the cardiovascular deaths, hypertensive heart failure accounted for 73.3%, whilst all heart failure cases accounted for 80.0%. Left ventricular hypertrophy was present in 69.2% of the patients with hypertensive heart disease. Moderate to severe atheromatous changes occurred in the aorta in 38.5% of patients aged ?50 years. No case of myocardial infarction was found.Hypertensive heart disease and hypertension-related disorders are the most common causes of sudden death in South West Nigeria, so effective public health strategies should be channeled towards prevention, detection, and treatment of hypertension. HubMed – drug

Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis.

Neuropsychiatr Dis Treat. 2013; 9: 893-914
Lugaresi A, di Ioia M, Travaglini D, Pietrolongo E, Pucci E, Onofrj M

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics. There is no single best treatment strategy, but therapy has to be tailored to the patient. This is a time-consuming task, rich in complexity, and influenced by the attitude towards risk on the parts of both the patient and the clinical team. The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for. HubMed – drug

Eldon Roberts – Salvation Army – Volunteer in PRofile 2009 – Eldon has volunteered with the Salvation Armys Kettle Campaign for 16 years. The Salvation Army Christmas Kettle Campaign raises money for the homeless, fami…