To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma ...and epithelioid hemangioendotheliomas.
In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days.
Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable.
Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.
HSP90 inhibition leads to proteosomal degradation of activated KIT and has in vitro activity against gastrointestinal stromal tumors (GIST). BIIB021 is an oral non-ansamycin HSP90 inhibitor. We ...carried out a phase II study of BIIB021 in patients with GIST refractory to imatinib and sunitinib.
The primary end-point was metabolic partial response (mPR) as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET). The secondary end-points were pharmacokinetic assessments of BIIB021 and pharmacodynamic assessments of HSP70. Twenty-three patients were treated on two schedules: 12pts received 600mg twice a week (BIW) and 11 patients received 400mg three times a week (TIW). All had prior imatinib and sunitinib but stopped >14 days before starting BIIB021.
The median age was 59 years (33–88 years), 61% male, 44% Eastern Cooperative Oncology Group 1 (ECOG1). The best response was PR by FDG-PET for five patients (3/12 at 600mg BIW and 2/9 at 400 TIW) for an overall response rate of 22%. The response duration was 25–138 days. Adverse events (AEs) were mild to moderate. The mean Cmax was 1.5µmol and the mean AUC was 2.9µmolh. Cmax >1.5µmol was associated with a decrease in standardized uptake value (SUVmax). HSP70 increased substantially following treatment.
This study met its primary end-point. BIIB021 leads to objective responses in refractory GIST patients. Pharmacodynamic studies confirmed HSP90 inhibition. Further evaluation of BIIB021 in GIST is warranted.
Background. Malnutrition is a common complication in haemodialysis patients. Recently, the Geriatric Nutritional Risk Index (GNRI) has been reported as a simple and accurate tool to assess ...nutritional status of haemodialysis patients. Our objective was to examine the association between GNRI and mortality in chronic haemodialysis patients. Methods. We examined the GNRI of 490 maintenance haemodialysis patients (60 ± 12 years, 293 males and 197 females) and followed up these patients for 60 months. Predictors for all-cause death were examined using Kaplan–Meier analysis and Cox proportional analyses. Results. The GNRI was 98.0 ± 6.0, and was significantly and negatively correlated with age and haemodialysis duration. During the 60-month follow-up period, 129 patients died. According to the highest positive likelihood and risk ratios, the cutoff value of GNRI for mortality was set at 90. Kaplan–Meier analysis revealed that patients with a GNRI <90 (n = 50) had a significantly lower survival rate, compared to those with GNRI ≥90 (n = 440) (log-rank test, P < 0.0001). Multivariate Cox proportional hazards analyses demonstrated that GNRI was a significant predictor for mortality hazard ratio (HR) 0.962, 95% confidence interval (CI) 0.931–0.995, P < 0.05, after adjustment for age, gender, C-reactive protein, presence of diabetes and haemodialysis duration. Conclusions. These results demonstrated that GNRI is a significant predictor for mortality in haemodialysis patients. The simple method of GNRI is considered to be a clinically useful marker for the assessment of nutritional status in haemodialysis patients.
Summary
Serum undercarboxylated osteocalcin (ucOC)/intact osteocalcin (iOC) ratio increased >1.0 in the patients undergoing hemodialysis, particularly in those with high bone turnover state. ...Consequently, serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in hemodialysis patients.
Introduction
Serum intact osteocalcin (iOC), undercarboxylated OC (ucOC), and the ucOC/iOC ratio are considered clinically relevant indices in pre-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, despite their accumulation in uremic serum.
Methods
Serum iOC and ucOC were measured along with serum intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRACP)-5b in 89 pre-dialysis CKD and 189 HD patients.
Results
Serum iOC and ucOC showed significantly negative correlations with estimated glomerular filtration rate in pre-dialysis CKD patients, although serum ucOC/iOC ratio did not correlate. Serum ucOC was significantly greater in HD patients than in pre-dialysis CKD patients, while serum iOC did not differ significantly, resulting in serum ucOC/iOC ratio >1.0 in 135 (71.4 %) out of 189 HD patients. HD patients with high serum ucOC/iOC ratio (>1.0) had a significantly younger age and significantly higher values of body mass index, serum creatinine, albumin, phosphate, iPTH, and TRACP-5b than those with low ucOC/iOC ratio (≤1.0). The baseline iPTH and P1NP correlated with the changes of the ucOC/iOC ratio during the 2 days of the inter-dialytic period. Multivariate analysis showed that log ucOC/iOC in HD patients was significantly associated with log iPTH, log BAP, or log TRACP-5b.
Conclusions
Serum ucOC/iOC ratio >1.0 was observed in as high as 71.4 % of HD patients, preferentially with high bone turnover state, in comparison with pre-dialysis CKD patients. These data suggested that serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in HD patients.
We have deposited Si-doped DLC (Si-DLC) multilayer films by plasma-enhanced chemical vapor deposition (PECVD) using an intermittent supply of monomethylsilane (SiH3CH3; MMS) as the Si source. The ...mechanical and tribological properties of the multilayer films were compared with those of Si-DLC single-layer films. The internal stress decreased as the Si content increased. It was found that the internal stress values of the multilayer films were lower than those of the single-layer films. Scratch tests demonstrated that the multilayer films had higher adhesion strength than the single-layer films owing to the further reduction of the internal stress. We found that the multilayer films with low Si content presented low friction while maintaining the wear performance. Specifically, the multilayer film containing ~2at.% Si showed a friction coefficient less than 0.08, while the addition of ~11at.% Si to the single-layer film was required for obtaining such a low friction coefficient. The wear rate increased with increasing Si content. In the case of the above two films, the single-layer film had a specific wear about rate two times higher than that of the multilayer film.
•The stresses of multilayer films were lower than those of single-layer films.•Multilayer films had higher adhesion strength than single-layer films.•Multilayer films showed better tribological properties than single-layer films.
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