A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts
Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113)...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2017
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| Sorozat: | LEUKEMIA
31 |
| doi: | 10.1038/leu.2017.159 |
| mtmt: | 3279788 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/16998 |
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| 024 | 7 | |a 3279788 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 2 | |a Garcia-Manero Guillermo | |
| 245 | 1 | 2 | |a A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts |h [elektronikus dokumentum] / |c Garcia-Manero Guillermo |
| 260 | |c 2017 | ||
| 300 | |a 2799-2806 | ||
| 490 | 0 | |a LEUKEMIA |v 31 | |
| 520 | 3 | |a Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.Leukemia advance online publication, 14 July 2017; doi:10.1038/leu.2017.159. | |
| 700 | 0 | 1 | |a Sekeres Mikkael A. |e aut |
| 700 | 0 | 1 | |a Egyed Miklós |e aut |
| 700 | 0 | 1 | |a Breccia Massimo |e aut |
| 700 | 0 | 1 | |a Graux Carlos |e aut |
| 700 | 0 | 1 | |a Cavenagh Jamie D. |e aut |
| 700 | 0 | 1 | |a Salman Huda S. |e aut |
| 700 | 0 | 1 | |a Illés Árpád |e aut |
| 700 | 0 | 1 | |a Fénaux Pierre |e aut |
| 700 | 0 | 1 | |a DeAngelo Daniel J. |e aut |
| 700 | 0 | 1 | |a Stauder Reinhard |e aut |
| 700 | 0 | 1 | |a Yee Karen W.L. |e aut |
| 700 | 0 | 1 | |a Zhu Nancy Y. |e aut |
| 700 | 0 | 1 | |a Lee Jae-hoon |e aut |
| 700 | 0 | 1 | |a Borbényi Zita |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/16998/1/2017_Phase1b2b_leukemia.pdf |z Dokumentum-elérés |