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- Glimelius, Bengt, et al.
(author)
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A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
- 2008
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
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Journal article (peer-reviewed)abstract
- Background: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m2 on day 1, 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m2 on day 1, FA 200 mg/m2, 5-FU bolus 400 mg/m2 and infused 5-FU 600 mg/m2 on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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- Lenzen, M., et al.
(author)
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Pharmacological treatment and perceived health status during 1-year follow up in patients diagnosed with coronary artery disease, but ineligible for revascularization. Results from the Euro Heart Survey on Coronary Revascularization
- 2006
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In: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 5:2, s. 115-121
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Journal article (peer-reviewed)abstract
- Background: It has been recognized that a clinically significant portion of patients with coronary artery disease (CAD) continue to experience anginal and other related symptoms that are refractory to the combination of medical therapy and revascularization. The Euro Heart Survey on Revascularization (EHSCR) provided an opportunity to assess pharmacological treatment and outcome in patients with proven CAD who were ineligible for revascularization. Methods: We performed a secondary analysis of EHS-CR data. After excluding patients with ST-elevation myocardial infarction and those in whom revascularization was not indicated, 4409 patients remained in the analyses. We selected two groups: (1) patients in whom revascularization was the preferred treatment option (n = 3777, 86%), and (2) patients who were considered ineligible for revascularization (n = 632, 14%). Results: Patient ineligible for revascularization had a worse risk profile, more often had a total occlusion (59% vs. 37%, p < 0.001), were treated more often with ACE-inhibitors (65% vs. 55%, p < 0.001) but less likely with aspirin (83% vs. 88%, p < 0.001). Overall, they had higher case-fatality at 1-year (7.0% vs. 3.7%, p < 0.001). Regarding self-perceived health status, measured via the EuroQol 5D (EQ-5D) questionnaire, these same patients reported more problems on all dimensions of the EQ-5D. Furthermore, in the revascularization group we observed an increase between discharge and 1-year follow up (utility score from 0.85 to 1.00) whereas patients ineligible for revascularization did not improve over time (utility score remained 0.80). Conclusion: In this large cohort of European patients with CAD, those considered ineligible for revascularization had more co-morbidities and risk factors, and scored worse on self-perceived health status as compared to revascularized patients in the revascularization group. With the exception of ACE-inhibitors and aspirin, there were no major differences regarding drug treatment between the two groups. Given these clinically significant observations, there appears to be a role for nurse-led, multidisciplinary, rehabilitation teams that target clinically vulnerable patients whose symptoms remain refractory to standard medical care. © 2006 European Society of Cardiology.
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- McEvoy, Brian P., et al.
(author)
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Geographical structure and differential natural selection among North European populations
- 2009
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:5, s. 804-814
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Journal article (peer-reviewed)abstract
- Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.
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- Villman, Kenneth, et al.
(author)
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TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer
- 2006
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In: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:5, s. 590-6
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Journal article (peer-reviewed)abstract
- The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).
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