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Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors.
Kim Appleton
1 ,
Helen J Mackay ,
Ian Judson ,
Jane A Plumb ,
Carol McCormick ,
Gordon Strathdee ,
Chooi Lee ,
Sophie Barrett ,
Sarah Reade ,
Dalal Jadayel ,
Adrian Tang ,
Katharine Bellenger ,
Lynsay Mackay ,
Albert Setanoians ,
Andreas Schätzlein ,
Chris Twelves ,
Stanley B Kaye ,
Robert Brown
Oct 10 2007
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Abstract
The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine) induces DNA demethylation and re-expression of epigenetically silenced genes, and increases carboplatin sensitivity of tumor xenograft models. We designed a clinical study to determine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be capable of producing equivalent biologic effects in patients with solid tumors.