Susan T. Arthur

Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer

PURPOSE c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor. METHODS Previously treated patients with EGFR TKI-naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required. RESULTS One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms. CONCLUSION The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned.

One-year prevalence, comorbidities and cost of cachexia-related inpatient admissions in the USA

Background: Cachexia is a condition characterized as a loss in body mass or metabolic dysfunction and is associated with several prevalent chronic health conditions including many cancers, COPD, HIV, and kidney disease, with between 10 and 50% of patients with these conditions having cachexia. Currently there is little research into cachexia and our objective is to characterize cachexia patients, their healthcare utilization, and associated hospitalization costs. Given the increasing prevalence of chronic diseases, it is important to better understand cachexia so that the condition can be better diagnosed and managed. Methods: We utilized one year (2009) of the Nationwide Inpatient Sample (NIS). The NIS represents all inpatient stays at a random 20% sample of all hospitals within the United States. We grouped cachexia individuals by primary or secondary discharge diagnosis and then compared those with cachexia to all others in terms of length of stay (LOS) and total cost. Finally we looked into factors predicting increased LOS using a negative binomial model. Results: We estimated US prevalence for cachexia-related inpatient admissions at 161,898 cases. Cachexia patients were older, with an average age of 67.95 versus 48.10 years in their non-cachexia peers. Hospitalizations associated with cachexia had an increased LOS compared to non-cachexia patients (6 versus 3 days), with average costs per stay

Factors influencing isometric exercise training-induced reductions in resting blood pressure.

4641.30 greater. Differences were seen in loss of function (LOF) with cachexia patients, mostly in the major LOF category (52.60%), whereas non-cachexia patients were spread between minor, moderate, and major LOF (36.28%, 36.11%, and 21.26%, respectively). Significant positive predictors of increased LOS among cachexia patients included urban hospital (IRR=1.21, non-teaching urban; IRR=1.23, teaching urban), having either major (IRR=1.41) or extreme (IRR=2.64) LOF, and having a primary diagnosis of pneumonia (IRR=1.15). Conclusion: We have characterized cachexia and seen it associated with increased length of stay, increased cost, and more severe loss of function in patients compared to those without cachexia.

Cachexia among US cancer patients

Hypertension is a major health concern, and current recommendations for blood pressure management (lifestyle modifications and pharmacological intervention) have not been universally successful. For two decades, isometric exercise training (IET) has become established as effective at reducing in resting BP (RBP) in a short period (4–10 weeks). The most common IET modes have comprised isometric handgrip (IHG) or isometric bilateral leg (IBL) training and 4 × 2‐min contractions at ∼20–50% maximal voluntary contraction with 1–5‐min rest between. Although this type of exercise training could have important implications, for hypertensive patients and in preventing hypertension development, little is known about the mechanisms responsible for IET‐induced RBP reductions. This uncertainty derives from a lack of understanding concerning the most effective IET programs for specific populations. Possible influential factors and mechanisms include age, sex, pre‐existing disease and medication, and IET‐induced adaptations in the exercising muscle and nervous system, which are discussed in this review. Designing effective IET programs may involve manipulation of exercise intensity, frequency, duration and mode, as well as consideration of yet discovered mechanisms for RBP reductions. We call for additional research designed to understand more about the mechanisms involved in IET‐induced RBP reductions for maximum effectiveness.

Healthcare utilization and costs associated with COPD among SEER-Medicare beneficiaries with NSCLC

Abstract Background: Cancer cachexia is a debilitating condition and results in poor prognosis. The purpose of this study was to assess hospitalization incidence, patient characteristics, and medical cost and burden of cancer cachexia in the US. Methods: This study used a cross-sectional analysis of the Nationwide Inpatient Sample (NIS) for 2009. Five cancers reported to have the highest cachexia incidence were assessed. The hospitalization incidence related to cachexia was estimated by cancer type, cost and length of stay were compared, and descriptive statistics were reported for each cancer type, as well as differences being compared between patients with and without cachexia. Results: Risk of inpatient death was higher for patients with cachexia in lung cancer (OR = 1.32; CI = 1.20–1.46) and in all cancers combined (OR = 1.76; CI = 1.67–1.85). The presence of cachexia increased length of stay in lung (IRR = 1.05; CI = 1.03–1.08), Kaposi’s sarcoma (IRR = 1.47; CI = 1.14–1.89) and all cancers combined (IRR = 1.09; CI = 1.08–1.10). Additionally, cachectic patients in the composite category had a longer hospitalization stay compared to non-cachectic patients (3–9 days for those with cachexia and 2–7 days for those without cachexia). The cost of inpatient stay was significantly higher in cachexic than non-cachexic lung cancer patients (

Mice Lacking PKCθ in Skeletal Muscle Have Reduced Intramyocellular Lipid Accumulation and Increased Insulin Responsiveness in Skeletal Muscle

13,560 vs

Cachexia & debility diagnoses in hospitalized children and adolescents with complex chronic conditions: evidence from the Kids' Inpatient Database.

13 190; p < 0.0001), as well as cachexic vs non-cachexic cancer patients in general (14 751 vs 13 928; p < 0.0001). Conclusions: Cachexia increases hospitalization costs and length of stay in several cancer types. Identifying the medical burden associated with cancer cachexia will assist in developing an international consensus for recognition and coding by the medical community and ultimately an effective treatment plans for cancer cachexia.

GSK3β inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running

Abstract Aim: To estimate the healthcare utilization and costs in elderly lung cancer patients with and without pre-existing chronic obstructive pulmonary disease (COPD). Methods: Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, this study identified patients with lung cancer between 2006–2010, at least 66 years of age, and continuously enrolled in Medicare Parts A and B in the 12 months prior to cancer diagnosis. The diagnosis of pre-existing COPD in lung cancer patients was identified using ICD-9 codes. Healthcare utilization and costs were categorized as inpatient hospitalizations, skilled nursing facility (SNF) use, physician office visits, ER visits, and outpatient encounters for every stage of lung cancer. The adjusted analysis was performed using a generalized linear model for healthcare costs and a negative binomial model for healthcare utilization. Results: Inpatient admissions in the COPD group increased for each stage of non-small cell lung cancer (NSCLC) compared to the non-COPD group per 100 person-months (Stage I: 14.67 vs 9.49 stays, p < .0001; Stage II: 14.13 vs 10.78 stays, p < .0001; Stage III: 28.31 vs 18.91 stays, p < .0001; Stage IV: 49.5 vs 31.24 stays, p < .0001). A similar trend was observed for outpatient visits, with an increase in utilization among the COPD group (Stage I: 1136.04 vs 796 visits, p < .0001; Stage II: 1325.12 vs 983.26 visits, p < .0001; Stage III: 2025.47 vs 1656.64 visits, p < .0001; Stage IV: 2825.73 vs 2422.26 visits, p < .0001). Total direct costs per person-month in patients with pre-existing COPD were significantly higher than the non-COPD group across all services (

Do Notch and mTOR Correlate for Myotube Formation In C2C12s?: 2260 Board #96 June 1 9

54,799.16 vs

Glycogen Enhancement Augments Overload-Induced Protein Synthesis, Growth, and Myogenesis in Aged Skeletal Muscle.: 2007 Board #268 May 31 2

41,862.91). Outpatient visits represented the largest cost category across all services in both groups, with higher costs among the COPD group (