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
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
36
References
127
Citations
NaN
KQI