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- Joerger, Markus, et al.
(author)
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Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients : a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group.
- 2007
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:21, s. 6410-6418
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Journal article (peer-reviewed)abstract
- Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 μmol/L (tC > 0.05−0.2) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. Experimental Design: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m2) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. Results: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel tC > 0.05 was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel tC > 0.05 > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel tC > 0.05 < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel tC > 0.05 was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (Cmax and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10−4). Conclusions: In this group of patients, paclitaxel tC > 0.05 is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.
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| 2. |
- Reeves, P., et al.
(author)
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The current and future burden and cost of overactive bladder in five European countries
- 2006
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In: Eur Urol. - : Elsevier BV. - 0302-2838. ; 50:5, s. 1050-7
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To estimate and compare the current and future direct cost of overactive bladder (OAB) to the health care systems of five European countries. METHOD: A health economic model was created to estimate the number of people currently affected by OAB symptoms, the expected number to be affected in the future, and the resultant economic burden on health care systems in Germany, Italy, Spain, Sweden, and the United Kingdom. RESULTS: The model estimated that in 2000, 20.2 million people over age 40 in the five countries experienced the symptoms of OAB; 7 million of these had urgency with urge incontinence. This figure is expected to rise to 25.5 million by 2020, including 9 million who will have urgency with urge incontinence. Average annual direct costs of OAB management ranged from euro269 to euro706 per patient per year. The largest cost was the use of incontinence pads, accounting for an average of 63% of the annual per patient cost of OAB management. Total cost to health care systems across all five countries was estimated at euro4.2 billion in 2000, and by 2020, the expected total cost was estimated to be euro5.2 billion, an increase of euro1 billion (26%). CONCLUSION: OAB is prevalent, with a substantial direct cost that is anticipated to increase in the future in line with aging populations. The overall burden, including indirect costs, may be considerably larger, and will fall predominantly on the elderly OAB population with urge incontinence. Recommended medical treatments could help manage those costs and should be evaluated.
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| 3. |
- Rich, Rebecca L., et al.
(author)
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A global benchmark study using affinity-based biosensors
- 2009
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In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Journal article (peer-reviewed)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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