The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

2.50
Hdl Handle:
http://hdl.handle.net/10541/69769
Title:
The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.
Authors:
Burnett, Alan K; Milligan, Donald W; Goldstone, Anthony H; Prentice, Archibald G; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith
Abstract:
The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.
Affiliation:
Department of Haematology, School of Medicine, Cardiff University Heath Park, Cardiff, UK. BurnettAK@Cardiff.ac.uk
Citation:
The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial. 2009, 145 (3):318-32 Br. J. Haematol.
Journal:
British Journal of Haematology
Issue Date:
May-2009
URI:
http://hdl.handle.net/10541/69769
DOI:
10.1111/j.1365-2141.2009.07604.x
PubMed ID:
19291085
Type:
Article
Language:
en
ISSN:
1365-2141
Appears in Collections:
All Christie Publications ; Haematology

Full metadata record

DC FieldValue Language
dc.contributor.authorBurnett, Alan K-
dc.contributor.authorMilligan, Donald W-
dc.contributor.authorGoldstone, Anthony H-
dc.contributor.authorPrentice, Archibald G-
dc.contributor.authorMcMullin, Mary-Frances-
dc.contributor.authorDennis, Michael-
dc.contributor.authorSellwood, Elizabeth-
dc.contributor.authorPallis, Monica-
dc.contributor.authorRussell, Nigel-
dc.contributor.authorHills, Robert K-
dc.contributor.authorWheatley, Keith-
dc.date.accessioned2009-06-05T10:18:00Z-
dc.date.available2009-06-05T10:18:00Z-
dc.date.issued2009-05-
dc.identifier.citationThe impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial. 2009, 145 (3):318-32 Br. J. Haematol.en
dc.identifier.issn1365-2141-
dc.identifier.pmid19291085-
dc.identifier.doi10.1111/j.1365-2141.2009.07604.x-
dc.identifier.urihttp://hdl.handle.net/10541/69769-
dc.description.abstractThe acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.en
dc.language.isoenen
dc.subjectAcute Myeloid Leukaemiaen
dc.subjectChemoresistanceen
dc.subjectP-Glycoproteinen
dc.subjectMyelodysplastic Syndromeen
dc.titleThe impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, School of Medicine, Cardiff University Heath Park, Cardiff, UK. BurnettAK@Cardiff.ac.uken
dc.identifier.journalBritish Journal of Haematologyen

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