Soft tissue sarcomas (STS) are rare tumours for which treatment options are limited in the advanced setting. Histone deacetylase inhibitors have shown activity in preclinical models of STS.
We ...conducted a single-arm, open-label, multicentre phase II study to assess the efficacy and tolerability of panobinostat given orally, 40 mg thrice weekly in patients with advanced pretreated STS. The primary endpoint was the 3-month progression-free rate.
Forty-seven STS patients were enrolled between January 2010 and December 2010. Median age was 59 (range 21-79) years, 22 (47%) patients were males. Panobinostat dose was lowered to 20 mg thrice weekly after nine patients were enrolled, based on the recommendation of an independent safety committee. The most common grade 3/4 adverse events were thrombocytopenia, fatigue, lymphopenia and anaemia. Forty-five patients were evaluable for the primary endpoint. Among them, nine patients (20%, 95% CI (10-35%)) were progression-free at 3 months. No partial response was seen, but 17 patients (36%) had stable disease (SD) as their best response. Six patients were progression-free at 6 months.
Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited, although some patients had prolonged SD.
Although sarcomas account for only 1% of all solid tumours, patients with sarcomas comprise a larger proportion of patients entering phase I trials, due to the limited number of registered or active ...drugs for these diseases. To help in patient selection, we evaluated the utility of the predictive Royal Marsden Score which had been derived in carcinoma patients. In addition, we analysed efficacy and toxicity regarding the sarcoma population enrolled in phase I trials.
We used data from a European Database comprising 2182 patients treated in phase I trials in 14 European institutions between 2005 and 2007.
One hundred and seventy-eight patients diagnosed with advanced sarcoma or other mesenchymal tumours were identified and accounted for 217 phase I trial participations during the study period. Histological type, class of drug, number of metastatic sites, high serum lactate dehydrogenase activity (LDH), low albumin and high white blood cell count were independent prognostic factors. Poor performance status (PS), liver metastases and high leucocyte count were associated with increased risk of early death. The class of drug used was the strongest predictor of progression-free survival (PFS) duration, inhibitors of angiogenesis and histone deacetylase giving the best results. Poor PS, high serum LDH and low lymphocyte count correlated with shorter PFS. In this heterogeneous population, PFS with investigational agents appeared comparable with that previously published for patients receiving standard treatments beyond first line.
Prognostic factors in sarcoma patients do not differ from a broader phase I population. Efficacy measures suggest that some patients with sarcoma derive benefit from therapy in this setting which could therefore be considered for patients with no remaining standard therapeutic option.
The combination platinum, 5-fluorouracil (5-FU) and cetuximab is the standard first-line regimen of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Due to the toxicity of ...this treatment, alternative therapies are often offered to patients. The aim of this study was to evaluate the overall survival obtained with a first line chemotherapy adapted to patients functional status and the administration of all active drugs within successive lines of chemotherapy.
This series included a total of 194 patients with recurrent and/or metastatic HNSCC treated from 2006 to 2011 in a single institution where the administration of successive lines of chemotherapies has been the standard clinical approach. Treatment was administered according to clinical practice guidelines.
Most patients received at least two treatment lines. Only 11 patients (6%) were treated with a combination of cisplatin, 5-FU and cetuximab in front line, but most patients received at least one platinum-based regimen (n = 154 patients, 78%); 162 (82%) received taxanes, 36 (18%) received 5-FU, 27 (14%) received capecitabine, 67 (34%) received methotrexate and 134 (68%) received cetuximab. The median overall survival was 9.8 months (95% CI: 8.1-11.4 months) and reached 13.1 months among the subgroup of 131 patients eligible for inclusion in a clinical trial.
The survival outcomes of patients treated in the first-line setting with chemotherapy regimens adapted to their functional status, followed by several subsequent regimens were comparable with published outcomes of patients treated by platinum, 5-FU and cetuximab.
The paper summarizes several years of research on the application of modem materials in the design of large steam turbines operating at high temperatures. The use of 9-12% chromium steels on main ...steam turbine components, the application of abradable coatings in seals and the seize/corrosion protection of selected components by modem surfacing techniques are presented. Results of materials long-term testing supported by the field application at elevated steam temperatures were used to verify the new material solutions and manufacturing techniques. The second section of the paper presents the design of a new 660 MW supercritical power plant to be built in the Czech Republic between 2008 and 2010. The unit parameters and steam cycle characteristics are presented together with the visualization of the new block. The steam turbine design is discussed with respect to the application of advanced materials.
A feedback method of digital measuring of the rate of statistically distributed pulses is described. The system adapts automatically to the situation at its input. If great changes of measured ...quantity are observed, the output follows these changes fast with greater standard deviation; later the first "estimation" of the value of measured quantity is further improved. The basic dynamic properties as well aa standard deviation both at transient and steady-state are described and dynamic properties of various methods of digital rate measuring are compared. The desoribed method of rate measuring can be applied also to digital measuring of relative rate n/no or of rate relative difference (n - no)/no.
Portrait of Puskin. Small graphic, mask, woman, writer, literature
Z knih M. Jancákové. Puskin arcképe mögött álarcát levevő nőalak. Anyag és technika: lino(leum)metszet
Kisgrafika, művészet, író, ...irodalom
Harvesting man.
Small graphics, art, clouds, farming, agricultural land
Arató férfi. Anyag és technika: lino(leum)metszet
Kisgrafika, művészet, felhők, földművelés, termőföld
PDF
