Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer

Background: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC.

Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m2 dose every three weeks

Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%.

Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

Use of electrochemical impedance spectroscopy for study of CO2 corrosion prevention by batch treatment inhibitor films

Electrochemical impedance spectroscopy (EIS) was used to study and evaluate commercial batch treatment inhibitors which are used for protecting oil wells, gas wells, and pipelines from CO2 corrosion, focusing on the evaluation of inhibitor film persistency. It was found that theformation and deterioration of batch treatment inhibitor films were accompanied by typical impedance spectral changes. During the formation of inhibitor films, electrode impedance showed a rapid increase and the Bode phase angle plots also showed a sudden change. Thus, the formation of inhibitor film was a very fast process. During the deterioration of inhibitor films, electrode impedance showed a gradual decrease and the Bode phase angle plots showed changes which characterised the three stages of the inhibitor film deterioration process. The relationships between EIS and corrosion rate are discussed, including comparisons with weight loss measurements. Based on the experimental findings in the present work, a method is suggested for estimating the persistency of inhibitor films by monitoring the characteristic changes in the Bode phase angle plots and by measuring electrochemical charge transfer resistance at the second and third stages of the inhibitor film deterioration process.

Monitoring batch treatment inhibitor performance continuously using electrochemical noise analysis

Electrochemical noise analysis (ENA) was used to monitor continuously the formation and deterioration processes of a commercial batch treatment inhibitor film of the type used for protecting against CO₂ corrosion in oilfields; ENA was shown to be able to follow effectively the formation and deterioration processes of batch treatment inhibitor films. As an inhibitor film formed, the current noise amplitude decreased rapidly and the noise resistance R_n, which is deducible from the voltage and current noise records, was found to increase sharply. Conversely, as the inhibitor film deteriorated, the current noise amplitude increased rapidly and R_n decreased rapidly. In the corrosion inhibition system studied, the noise resistance was confirmed to be similar to the linear polarisation resistance. Based on the calculation of R_n on a continuous basis, a technique is proposed to study fast corrosion processes.

Effects of the aromatase inhibitor Fadrozole on plasma sex steroid secretion and oocyte maturation in female coho salmon (Oncorhynchus kisutch) during vitellogenesis

17β-estradiol, 17α-20β-dihydroxy-4-pregnen-3-one (17α-20β-P), and testosterone levels were measured in plasma samples obtained from vitellogenic coho salmon (Oncorhynchus kisutch) before and 32 days after injection of the aromatase inhibitor Fadrozole (AI). Plasma 17β-estradiol levels decreased significantly 6 h after injection in all AI treated fish. The higher the dose the longer the maintenance of low plasma 17β-estradiol levels. Inversely, plasma 17α-20β-P increased significantly 6 h after injection in all AI treated fish, and the higher the dose the longer the maintenance of high plasma 17α-20β-P levels. At 48 h after injection plasma testosterone levels were significantly higher in the AI treated groups. The oocyte maturation index showed that multiple injections with AI retarded oocyte development. Besides, oocyte diameter and GSI were lower in the same group, which presented high incidence of atresia of vitellogenic oocytes. The ovarian follicles and brain of the fish which received multiple injections secreted less 17β-estradiol, in vitro. These findings suggest that aromatase inhibitors such as Fadrozole may have a potential as a tool to regulate sexual development in salmon.

Electrochemical methods applied in innovative corrosion inhibitor experiments : case studies

Electrochemical methods can be used more effectively if innovative experiments are designed and employed. This is especially true if a corrosion system to be tested involves inhibitors that could change the mechanism and pattern of corrosion in complex ways. This paper discusses corrosion inhibitor test design using several practical cases as examples. Particular attention is on difficult issues such as the simulation of localized corrosion phenomena and the influence of corrosion mechanism on inhibitor test results. ©2012 by NACE International.