Reviews on Recent Clinical Trials - Volume 5, Issue 1, 2010

There is overwhelming evidence that smoking cessation, regular physical activity, and combined dietary changes are beneficial in patients with coronary heart disease. Effect size estimates for these lifestyle goals vary between 20% and 35% of mortality rate reductions. Despite the evidence, achieving healthy lifestyles remains the most difficult problem in secondary prevention. In this paper, I review the effects of lifestyle changes on the clinical outcome of patients with coronary heart disease and the underlying mechanisms of benefit, as well as two recently published, controlled, clinical trials addressing the issue of achieving therapeutic lifestyle changes in coronary heart disease patients.

Glioblastoma (GBM), a WHO grade IV malignant glioma, is the most common and lethal adult primary brain tumor. Median survival rates range from 12-15 months. The current standard of care for GBM has evolved from resection followed by adjuvant radiotherapy to resection, concurrent adjuvant chemotherapy (temozolomide) and radiation, and additional adjuvant chemotherapy. The expression of specific molecular biomarkers, especially O-6 -methylguanine methyltransferase (MGMT) status, may determine the response of the tumor to treatment, and helps in identifying the magnitude of benefit from this regimen. By identifying further biological subtypes of GBM at the molecular level, specific targeted therapies could be developed and used in the future for more individualized therapeutic regimens. This article will review the current therapies for GBM and the investigation of new molecular and targeted therapies, such as EGFR inhibitors, mTOR/PI3Kinase inhibitors, and anti-angiogenesis agents.

Renal artery stenosis is the most common cause of secondary hypertension after exclusion of renal parenchymal disease and/or hypertensive nephrosclerosis. Atherosclerotic processes comprise the major contributors to this condition and account for 90% of the disease burden. Usually, the disease comes to light when there has been substantial morbidity resulting from several years of uncontrolled blood pressures and renal failure. Early recognition and intervention is warranted. Interventions include both medical and surgical modalities. Currently, there are several reliable diagnostic procedures to identify renal artery stenosis. However, once the disease process is identified, the management differs quite dramatically based on the patient population, the goals of therapy such as control of hypertension versus amelioration of ischemic nephropathy, availability of interventionists and so on. In this review, we discuss the importance of identifying atherosclerotic renal artery stenosis, the diagnostic modalities available and some of the interventions used to manage this disorder. We emphasize evidence based medicine and recent clinical trials such as the STAR trial.

Obstructive sleep apnea-hypoapnea syndrome (OSA) is a disorder that results in repetitive occlusion of the airway and hypoxemia during sleep. Epidemiologic studies have associated this disorder with increased cardiovascular morbidity and mortality. Systemic hypertension is prevalent among patients with OSA and it has been recognized as a common identifiable cause of hypertension. Nasal continuous positive airway pressure (nCPAP) ventilation is an effective therapy for OSA and may also reduce blood pressure. The use of nCPAP ventilation to treat hypertension in patients with OSA has been studied extensively. However, whether it is effective in treating hypertension in this population remains unclear. This review evaluates the recent literature that investigates the effects of nCPAP ventilation on hypertension in patients with OSA.

Advanced pancreatic cancer is usually treated with first-line gemcitabine (GEM) (alone or in combination). More recently, GEM has become an established part of an adjuvant therapy based on two recently-reported randomized trials. There remains unresolved the problem of second-line therapy in patients relapsed during or after adjuvant or firstline GEM-based treatment. As of today, platinum analogues in combination with fluoropyrimidine or with GEM represent the most common schedule in clinical practice with data from single-centre or multicentric phase II studies. In 2008, for the first time, a randomized phase III trial conducted on good performance status GEM-refractory patients (CONKO 003) confirmed their benefit in progression-free and overall survival by adding oxaliplatin to a bolus 5-FU/folinic acid schedule. Other agents (irinotecan, taxanes, antifolates, biological) have been tested, although only dismal results have been achieved, as they turned out to be too toxic in combination and to have too low activity when used as single agents. Which is the optimal candidate for second-line therapies, is debatable. Good performance status and discrete progressionfree survival since the beginning of the GEM therapy (more than 6 months?) are likely to be the best indicators of subsequent line benefit. The benefit of biological agents is unknown, also given the poor results achieved in the first-line treatment. In summary, as of today, there is one randomized study that confirms the benefit of second-line chemotherapy for the treatment of GEM-relapsed pancreatic cancer. Current data indicate 5-FU plus a platinum agent (oxaliplatin) as the standard of care for PS 0-1 patients. Ongoing clinical trials will clarify whether there is obviously a place for improvement and for other agents. At present, even though no data on benefits in unfit patients (Karnofsky < 70) are available, a fluopyrimidine agent still remains a reasonable treatment option.

Therapies that are believed to target the underlying mechanisms of Alzheimer's disease have now reached human clinical trials, with the number of agents in late stage development having increased dramatically in recent years. Primary targets include beta-amyloid, whose presence and accumulation in the brain is thought to contribute to the development of Alzheimer's disease, and tau protein which, when hyperphosphorylated, results in the formation of neurofibrillary tangles of paired helical filaments, also believed to be involved in the pathogenesis of Alzheimer's disease. In the review, the current status of Alzheimer's Disease therapies under study is discussed, including the scientific basis for each strategy.

Objective The consequences of Major Depressive Disorder (MDD) in youths are likely to be devastating for both the patient and his/her family. Thus, this review analyzes systematically the effectiveness of antidepressant drugs (ADDs) in managing such patients. Data Sources Medical literature reporting primary data on use of ADDs in children and adolescents was identified through searches (1966-January 2010) of MEDLINE/PubMed, EMBASE, SCOPUS, and The Cochrane Library databases. Additional studies were manually identified from the reference lists of published articles. Search Strategy Search terms (variously combined) were: children, childhood, adolescents, adolescence, MDD, mood/affective disorders, depression, tricyclic antidepressants (TCAs) SSRIs, Serotonin-Norepinephrine Reuptake inhibitors (SNRIs), noradrenergic/ specific serotoninergic antidepressants (NaSSA). A separate search was conducted to complete the profile of effectiveness of each single antidepressant agent. Data Selection 43 peer-reviewed articles met the inclusion criteria. Data Synthesis Reviewed information does not definitively support the use of antidepressants in children younger than 10 years old. In contrast, robust information suggests that fluoxetine should be considered as first-line agent in depressed adolescents whose clinical conditions require psychopharmacological approach. Conclusions Depressed children should be primarily approached with non-pharmacological interventions that should include the evaluation of potential parental psychiatric disorders. In adolescents with MDD, the decision to use fluoxetine should be associated with specific social and health protocols focused to reinforce self-esteem, improve the quality of relationships with parents and peers, facilitate healthy life-style changes, and identify the potential onset/worsening of suicidality.