title: Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na.
abstract: In a Phase I/II clinical trial, 13 higher risk red blood cell-dependent myelodysplastic syndrome (MDS) patients unresponsive to hypomethylating therapy were treated with the multikinase inhibitor ON 01910.Na. Responses occurred in all morphologic, prognostic risk and cytogenetic subgroups, including four patients with marrow complete responses among eight with stable disease, associated with good drug tolerance. In a subset of patients, a novel nanoscale immunoassay showed substantially decreased AKT2 phosphorylation in CD34+ marrow cells from patients responding to therapy but not those who progressed on therapy. These data demonstrate encouraging efficacy and drug tolerance with ON 01910.Na treatment of higher risk MDS patients.
authors.affiliation: Department of Medicine (Hematology), Stanford University Cancer Center, Stanford, CA, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Seetharam
authors.forename: Alice C
authors.initials: AC
authors.lastname: Fan
authors.forename: Mai
authors.initials: M
authors.lastname: Tran
authors.forename: Liwen
authors.initials: L
authors.lastname: Xu
authors.forename: John P
authors.initials: JP
authors.lastname: Renschler
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
authors.forename: Kunju
authors.initials: K
authors.lastname: Sridhar
authors.forename: Francois
authors.initials: F
authors.lastname: Wilhelm
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012306:Risk; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013450:Sulfones; C507134:ON 01910; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D005998:Glycine