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- Barrett-Lee, Peter J., et al.
(author)
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Independent risk factors for anemia in cancer patients receiving chemotherapy : results from the European Cancer Anaemia Survey
- 2006
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In: Oncology. - : S. Karger AG. - 0030-2414 .- 1423-0232. ; 70:1, s. 34-48
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To develop a hitherto unavailable risk factor model for accurately predicting anemia development in cancer patients before chemotherapy (CT) administration. METHODS: 2,070 nonanemic patients from the European Cancer Anaemia Survey (ECAS) with hemoglobin (Hb) > or =12 g/dl at enrollment who received their first CT during ECAS and underwent at least two CT cycles were divided randomly into split half (SH) 1 and SH2 (n = 1,035 each). The model was developed on SH1 using logistic regression to simultaneously evaluate predictive factors, and was validated using SH2 and an additional similar subpopulation of 5,901 ECAS patients. Anemia risk values were assigned to the predictive factors and the sum of the predictive factors gave the total anemia risk score; lower-, higher-, and highest-risk cutoff points of the total anemia risk score were determined. RESULTS: Variables ultimately identified as significant predictive factors for anemia were: lower initial Hb (< or =12.9 g/dl in females, and < or =13.4 g/dl in males); having lung or gynecologic cancer versus gastrointestinal (GI)/colorectal cancer; cancer at any other site versus GI/colorectal cancer; treatment with platinum CT, and female gender. CONCLUSION: Using this evidence-based risk model, nonanemic patients who are at the highest risk of developing anemia prior to receiving CT can be identified clinically, allowing appropriate anemia management to be planned.
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| 2. |
- van Erp, Nielka P, et al.
(författare)
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Influence of CYP3A4 Inhibition on the Steady-State Pharmacokinetics of Imatinib
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:24, s. 7394-7400
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the effects of ritonavir, a potent inhibitor of CYP3A4, on the steady-state pharmacokinetics of imatinib. Experimental Design: Imatinib pharmacokinetics were evaluated in cancer patients receiving the drug for at least 2 months, after which ritonavir (600 mg) was administered daily for 3 days. Samples were obtained on the day before ritonavir (day 1) and on the third day (day 4).The in vitro metabolism of imatinib with or without ritonavir and the effect of imatinib on 1-OH-midazolam formation rate, a probe for CYP3A4 activity, were evaluated with human CYP3A4 and pooled liver microsomes. Results: In 11 evaluable patients, the geometric mean (95% confidence interval) area under the curve of imatinib on days 1 and 4 were 42.6 (33.0-54.9) mu g.h/mL and 41.2 (32.1-53.1) mu g.h/mL, respectively (P = 0.65). A population analysis done in NONMEM with a time-dependent covariate confirmed that ritonavir did not influence the clearance or bioavailability of imatinib. In vitro, imatinib was metabolized to the active metabolite CGP74588 by CYP3A4 and CYP3A5 and, to a lesser extent, by CYP2D6. Ritonavir (1 mu mol/L) completely inhibited CYP3A4-mediated metabolism of imatinib to CGP74588 but inhibited metabolism in microsomes by only 50%. Imatinib significantly inhibited CYP3A4 activity in vitro. Conclusion: At steady state, imatinib is insensitive to potent CYP3A4 inhibition and relies on alternate elimination pathways. For agents with complex elimination pathways that involve autoinhibition, interaction studies that are done after a single dose may not be applicable when drugs are administered chronically.
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