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- Glimelius, Bengt, et al.
(författare)
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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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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
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Tidskriftsartikel (refereegranskat)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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- McEvoy, Brian P., et al.
(författare)
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Geographical structure and differential natural selection among North European populations
- 2009
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:5, s. 804-814
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Tidskriftsartikel (refereegranskat)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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