| Autor: |
Garcia-Manero, G, Sekeres, M A, Egyed, M, Breccia, M, Graux, C, Cavenagh, J D, Salman, H, Illes, A, Fenaux, P, DeAngelo, D J, Stauder, R, Yee, K, Zhu, N, Lee, J-H, Valcarcel, D, MacWhannell, A, Borbenyi, Z, Gazi, L, Acharyya, S, Ide, S, Marker, M, Ottmann, O G |
| Zdroj: |
Leukemia; December 2017, Vol. 31 Issue: 12 p2799-2806, 8p |
| Abstrakt: |
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. |
| Databáze: |
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| Externí odkaz: |
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