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- Parker, C., et al.
(author)
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Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
- 2013
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:3, s. 213-223
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Journal article (peer-reviewed)abstract
- Background Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. Methods In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. Results At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. Conclusions In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)
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- Hodnebrog, O., et al.
(author)
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Impact of forest fires, biogenic emissions and high temperatures on the elevated Eastern Mediterranean ozone levels during the hot summer of 2007
- 2012
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:18, s. 8727-8750
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Journal article (peer-reviewed)abstract
- The hot summer of 2007 in southeast Europe has been studied using two regional atmospheric chemistry models; WRF-Chem and EMEP MSC-W. The region was struck by three heat waves and a number of forest fire episodes, greatly affecting air pollution levels. We have focused on ozone and its precursors using state-of-the-art inventories for anthropogenic, biogenic and forest fire emissions. The models have been evaluated against measurement data, and processes leading to ozone formation have been quantified. Heat wave episodes are projected to occur more frequently in a future climate, and therefore this study also makes a contribution to climate change impact research. The plume from the Greek forest fires in August 2007 is clearly seen in satellite observations of CO and NO2 columns, showing extreme levels of CO in and downwind of the fires. Model simulations reflect the location and influence of the fires relatively well, but the modelled magnitude of CO in the plume core is too low. Most likely, this is caused by underestimation of CO in the emission inventories, suggesting that the CO/NOx ratios of fire emissions should be re-assessed. Moreover, higher maximum values are seen in WRF-Chem than in EMEP MSC-W, presumably due to differences in plume rise altitudes as the first model emits a larger fraction of the fire emissions in the lowermost model layer. The model results are also in fairly good agreement with surface ozone measurements. Biogenic VOC emissions reacting with anthropogenic NOx emissions are calculated to contribute significantly to the levels of ozone in the region, but the magnitude and geographical distribution depend strongly on the model and biogenic emission module used. During the July and August heat waves, ozone levels increased substantially due to a combination of forest fire emissions and the effect of high temperatures. We found that the largest temperature impact on ozone was through the temperature dependence of the biogenic emissions, closely followed by the effect of reduced dry deposition caused by closing of the plants' stomata at very high temperatures. The impact of high temperatures on the ozone chemistry was much lower. The results suggest that forest fire emissions, and the temperature effect on biogenic emissions and dry deposition, will potentially lead to substantial ozone increases in a warmer climate.
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- Tandstad, T., et al.
(author)
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One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group
- 2014
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:11, s. 2167-2172
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Journal article (peer-reviewed)abstract
- The SWENOTECA group treated 517 clinical stage I nonseminoma patients with one course of adjuvant BEP in a prospective study. The median follow-up is 7.9 years. One course of adjuvant BEP reduced the risk of relapse by over 90%. The relapse rates were 1.6% in low-risk disease and 3.2% in high-risk disease. One course of adjuvant BEP should be considered a standard adjuvant treatment option.SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.
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