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

Burnett, Alan Kenneth, Milligan, D., Goldstone, A., Prentice, A., McMullin, M. F., Dennis, M., Sellwood, E., Pallis, M, Russell, N., Hills, Robert Kerrin ORCID: https://orcid.org/0000-0003-0166-0062 and Wheatley, K. 2009. 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. British Journal of Haematology 145 (3) , pp. 318-332. 10.1111/j.1365-2141.2009.07604.x

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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/m2 vs. 35 mg/m2; (ii) Cytarabine 200 mg/m2 vs. 400 mg/m2 in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m2 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Wiley-Blackwell
ISSN:	0007-1048
Last Modified:	24 Oct 2022 11:55
URI:	https://orca.cardiff.ac.uk/id/eprint/49747

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