Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again.

The recent emergence of targeted and immunotherapeutic agents has dramatically changed the management for patients with non-small cell lung cancer (NSCLC). Despite these advances, lung cancer is not exempt from the challenges facing oncology drug development, including the huge financial cost and the time required for drug implementation. Repositioning noncancer therapies with potential antineoplastic properties into new therapeutic niches is an alternative treatment strategy offering the possibility of saving money and time and improving outcomes. The goal of such a strategy is to deliver an effective drug with a favorable toxicity profile at a reduced cost. Preclinical models and observational data have demonstrated promising activity for many of these agents, and they are now being studied in prospective trials. We review the relevant published data regarding the therapeutic effects of metformin, statins, nonsteroidal anti-inflammatory drugs, ß-blockers, and itraconazole in NSCLC, with a focus on the putative mechanisms of action and clinical data. As these drugs are increasingly being tested in clinical trials, we aim to highlight the salient challenges and future strategies to optimize this approach.

Tailoring Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Recent Advances and Strategies.

Neoadjuvant HER2 Therapy: Beyond one-size-fits-all.

Mortality after nasogastric tube feeding initiation in long-term care elderly with oropharyngeal dysphagia--the contribution of refeeding syndrome.

BACKGROUND: The refeeding syndrome (RS) is an underappreciated but clinically important entity characterized by acute electrolyte abnormalities, mainly hypophosphatemia, fluid retention and dysfunction of various organs and systems, which can result in significant morbidity and occasionally death. OBJECTIVE: To examine the incidence of death cases and death causes following nasogastric tube (NGT) feeding initiation in frail elderly with particular reference to RS. METHODS: Forty patients with feeding problems for at least 72 h before restarting of alimentation by NGT were included. Excluded were those in any critical clinical situation. Clinical parameters and nutritional assessment were recorded before and after refeeding. Blood samples were taken before, daily for the first 3 days and 1 week after refeeding initiation. RESULTS: During the 1st week of refeeding, 9 patients (22.5%) died and within 1 month 10 more, summing to 47.5%. Most deaths were due to infectious causes [15 out of 19, (79%)]; some were due to no obvious reason [4 out of 19, (21%)]. Significant electrolyte changes were observed in the 2-3 days following refeeding. Significant were the decreases in phosphorus and elevations in potassium and lymphocytes (day 7). We found no correlations between the severity of decreases in levels of phosphorus and mortality. CONCLUSIONS: Mortality after NGT feeding initiation was high, mainly due to infectious complications. However, in a considerable number of patients hypophosphatemia was noted, suggesting that RS could be a contributory factor of mortality. Since this is a treatable condition, more attention should be paid to detecting and coping with this problem.

Analysis of clinical symptomatology, extrapyramidal symptoms and neurocognitive dysfunction following dehydroepiandrosterone (DHEA) administration in olanzapine treated schizophrenia patients: a randomized, double-blind placebo controlled trial.

Several studies have demonstrated the effective use of dehydroepiandrosterone (DHEA) in the management of mood, however studies of its use in psychosis remain limited. The aim of this study was to investigate for the first time efficacy of DHEA augmentation with standardized antipsychotic medication (olanzapine) and to explore effects of DHEA augmentation on side-effect profiles including weight gain, glucose tolerance, aggression, quality of life and neurocognitive function. Finally, we aimed to analyze any relationship between plasma levels and clinical response to DHEA administration. Forty patients with chronic schizophrenia stabilized on olanzapine were randomized in double-blind fashion to receive either DHEA (titrated up to 150mg) or placebo augmentation for a period of 12-weeks. Blood samples were collected at baseline, mid-study and study completion. Results indicated improvement of negative symptoms (SANS scale) even when baseline scores were controlled as a covariate. Some improvement in Parkinsonism and akathisia compared to baseline was seen in patients receiving DHEA. No change in psychosis as reflected by the PANSS was noted. Patients receiving DHEA appeared to demonstrate relatively stable glucose levels compared to controls at the end of the study. An improvement in cognitive performance (most notably memory), which did not reach significance due to low sample number, was observed following DHEA administration. Results further suggest preliminary evidence of involvement of the neurosteroid system in schizophrenia pathophysiology, and confirm initial "cautious" findings identifying an agent capable of improving negative symptoms and certain features of extrapyramidal side effects.

Association of the RGS2 gene with extrapyramidal symptoms induced by treatment with antipsychotic medication.

OBJECTIVES: To investigate the role of genes encoding regulators of G protein signaling in early therapeutic response to antipsychotic drugs and in susceptibility to drug-induced extrapyramidal symptoms. As regulators of G protein signaling and regulators of G protein signaling-like proteins play a pivotal role in dopamine receptor signaling, genetically based, functional variation could contribute to interindividual variability in therapeutic and adverse effects. METHODS: Consecutively hospitalized, psychotic patients with Diagnostic and Statistical Manual of Mental Disorder-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (n=72) or typical antipsychotic drugs and risperidone (n=49) for at least 2 weeks. Clinical state and adverse effects were rated at baseline and after 2 weeks. Twenty-four single nucleotide polymorphisms were genotyped in five regulators of G protein signaling genes. RESULTS: None of the single nucleotide polymorphisms were related to clinical response to antipsychotic treatment at 2 weeks. Five out of six single nucleotide polymorphisms within or flanking the RGS2 gene were nominally associated with development or worsening of parkinsonian symptoms (PARK+) as measured by the Simpson Angus Scale, one of them after correction for multiple testing (rs4606, P=0.002). A GCCTG haplotype encompassing tagging single nucleotide polymorphisms within and flanking RGS2 was significantly overrepresented among PARK+ compared with PARK--patients (0.23 vs. 0.08, P=0.003). A second, 'protective', GTGCA haplotype was significantly overrepresented in PARK--patients (0.13 vs. 0.30, P=0.009). Both haplotype associations survive correction for multiple testing. CONCLUSIONS: Subject to replication, these findings suggest that genetic variation in the RGS2 gene is associated with susceptibility to extrapyramidal symptoms induced by antipsychotic drugs.