3051 Background: Ganetespib is a potent, next-generation Hsp90 inhibitor that is structurally unrelated to the first-generation ansamycin class of Hsp90 inhibitors and has shown superior activity to these agents in preclinical studies. It has been well tolerated and shown promising antitumor activity in early trials in multiple cancers. Preclinical data indicate that different client proteins show disparate expression kinetics upon Hsp90 inhibition. Therefore, twice-weekly dosing may be needed in some tumor types. Methods: Patients (pts) with solid tumors who have exhausted standard treatment options received ganetespib as a 1 hr infusion twice weekly for 3 weeks (wks) of a 28 day cycle until disease progression. Serial PK and pharmacodynamic samples were obtained during cycle 1. Safety assessments included frequency and grade of AEs, laboratory parameters and ECG changes. Results: Data are presented for 49 pts (22 M, 27 F; median age 55 yrs, range 32-81; ECOG status range 0-2) treated at doses from 2-144 mg/m2. Pts received a median of 2 (range 1-12) cycles of ganetespib. AEs reported in ≥20% of pts treated at doses from 2-120 mg/m2 are fatigue, diarrhea, nausea, anemia, abdominal pain, constipation, anorexia, vomiting, and headache; the majority of events were mild to moderate in severity with absence of severe liver, ocular, cardiac and renal toxicity. Two DLTs (elevated transaminases) have been reported in the 10 and 144 mg/m2 cohorts; expansion of the latter cohort is ongoing. Ganetespib shows linear PK, rapid distribution, a mean terminal half-life of 10-14 hours, a volume of distribution greater than total body water and no accumulation in plasma. HSP70 plasma protein levels will be presented. A confirmed durable PR by RECIST has been seen in a pt with metastatic melanoma. Additionally, 2 NSCLC pts who received 6 months of treatment had durable SD, with tumor shrinkage. Conclusions: Ganetespib has been well tolerated at dose levels up to 120 mg/m2 administered twice weekly. Preliminary safety profile, activity signals and differences in client protein kinetics warrant continued evaluation of ganetespib using a twice-weekly dosing regimen. Dose escalation continues.
Background: The national utilization rates and trends of pericardiocentesis and pericardiotomy are unknown. The objective of this observational study was to characterize the trends and in-hospital mortality of pericardiocentesis and pericardiotomy in the United States. Methods: The Nationwide Inpatient Sample (NIS) database was used to identify patients who underwent pericardiocentesis or pericardiotomy from 2005 to 2009. We evaluated their in-hospital mortality and used risk adjusted logistic regression to analyze the predictors of adverse outcomes including death. Results: A total of 131,945 patients underwent either pericardiocentesis or pericardiotomy during these five years. Pericardiocentesis was done in 49,854(37.8%) and pericardiotomy was done in 82,090 (62.2%). The per annum pericardiocentesis rate increased from 9,171 in 2005 to 11,088 in 2009 (20.9% increase) whereas the pericardiotomy rates were essentially the same during the study period. The risk adjusted in-hospital mortality was significantly higher in the pericardiocentesis group than in the pericardiotomy group (15.5% versus 10.3% p<0.001). Conclusion: In this observational study, we found that during the five-year study period the rates of pericardiocentesis significantly increased while pericardiotomy rates remained unchanged. The risk adjusted in-hospital mortality was significantly higher with pericardiocentesis than pericardiotomy.
In a healthy individual, there is 15–50 mL of fluid between the visceral and parietal layers of the fibroelastic pericardium. The normal composition of pericardial fluid is currently ill-defined. In the USA, pericardiocentesis is performed in patients with pericardial disease approximately 1000 times per month.1 2 During pericardiocentesis fluid is almost uniformly sent for laboratory analysis per guideline recommendations to quantify general chemistry and cellular composition.3 To date, there is no established methodology to assess pericardial fluid composition nor are there recognised reference values for the normal constituents of pericardial fluid. Interpretation of pericardial fluid composition is commonly performed by extending the Light’s criteria validated on pleural fluid analysis to pericardial fluid.3 4 The accuracy of this approach to establish if pericardial fluid is transudative or exudative is unknown.
Available data regarding the biochemical and cellular composition of physiological pericardial fluid are sparse. In a study of 30 consecutive patients without pericardial disease undergoing coronary artery bypass grafting or valvular replacement that underwent pericardial fluid analysis, mean fluid lactate …
