| 1. |
- Druker, Brian J., et al.
(författare)
-
Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
- 2006
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
|
|
| 2. |
|
|
| 3. |
- Kantarjian, Hagop M, et al.
(författare)
-
Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase.
- 2009
-
Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 115:3, s. 551-60
-
Tidskriftsartikel (refereegranskat)abstract
- Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response.
|
|
| 4. |
- Klein, Richard J.T., et al.
(författare)
-
Portfolio screening to support the mainstreaming of adaptation to climate change into development assistance
- 2007
-
Ingår i: Climate change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 84:1, s. 23-44
-
Tidskriftsartikel (refereegranskat)abstract
- The need to mainstream adaptation to climate change into development planning and ongoing sectoral decision-making is increasingly recognised, and several bilateral and multilateral development agencies are starting to take an interest. Over the past years at least six development agencies have screened their project portfolios, generally with two goals in mind: (1) to ascertain the extent to which existing development projects already consider climate risks or address vulnerability to climate variability and change, and (2) to identify opportunities for incorporating climate change explicitly into future projects. As each portfolio screening was conducted independently, the broader lessons emerging from the screenings have not been systematically analysed. In this paper we assess the screening activities to date, focusing on both the results and the methods applied. Based on this assessment we identify opportunities for development agencies to expand their current focus on the links between climate and development. Most agencies already consider climate change as a real but uncertain threat to future development, but they have given less thought to how different development patterns might affect vulnerability to climate change. The screenings undertaken have shown the need to take a comprehensive approach to adaptation and its integration into development planning and sectoral decision-making, and a number of policy initiatives have been taken to promote such integration. We provide some initial guidance as to how portfolio screening can be carried out in a way that would allow agencies to assess systematically the relevance of climate change to their ongoing and planned development projects.
|
|
| 5. |
- Larson, Richard A, et al.
(författare)
-
Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study.
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:8, s. 4022-8
-
Tidskriftsartikel (refereegranskat)abstract
- Imatinib at 400 mg daily is standard treatment for chronic myeloid leukemia in chronic phase. We here describe the correlation of imatinib trough plasma concentrations (C(mins)) with clinical responses, event-free survival (EFS), and adverse events (AEs). Trough level plasma samples were obtained on day 29 (steady state, n = 351). Plasma concentrations of imatinib and its metabolite CGP74588 were determined by liquid chromatography/mass spectrometry. The overall mean (+/- SD, CV%) steady-state C(min) for imatinib and CGP74588 were 979 ng/mL (+/- 530 ng/mL, 54.1%) and 242 ng/mL (+/- 106 ng/mL, 43.6%), respectively. Cumulative estimated complete cytogenetic response (CCyR) and major molecular response (MMR) rates differed among the quartiles of imatinib trough levels (P = .01 for CCyR, P = .02 for MMR). C(min) of imatinib was significantly higher in patients who achieved CCyR (1009 +/- 544 ng/mL vs 812 +/- 409 ng/mL, P = .01). Patients with high imatinib exposure had better rates of CCyR and MMR and EFS. An exploratory analysis demonstrated that imatinib trough levels were predictive of higher CCyR independently of Sokal risk group. AE rates were similar among the imatinib quartile categories except fluid retention, rash, myalgia, and anemia, which were more common at higher imatinib concentrations. These results suggest that an adequate plasma concentration of imatinib is important for a good clinical response. This study is registered at http://clinicaltrials.gov as NCT00333840.
|
|
