Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia
Por:
DeAngelo, DJ, Walker, AR, Schlenk, RF, Sierra, J, Medeiros, BC, Ocio, EM, Rollig, C, Strickland, SA, Thol, F, Valera, SZ, Dasgupta, K, Berkowitz, N, Stuart, RK
Publicada:
1 oct 2019
Resumen:
The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combination with idarubicin and cytarabine in newly diagnosed patients aged <= 65 years with primary or secondary high-risk AML based on cytogenetic classification. Treatment included fixed dose idarubicin (12 mg/m(2)/d, IV; day 1-3) and cytarabine (100 mg/m(2)/d, continuous IV infusion; day 1-7) and escalating oral doses of panobinostat at 15 mg, 20 mg, and 25 mg, thrice weekly starting at week 2 of a 28-day cycle. Forty-six patients were enrolled (primary AML [n = 36], secondary AML [n = 10]). The median age was 55 years. The most common all-grade AEs were diarrhea (54.3%), nausea (39.1%), vomiting, and decreased appetite (each, 21.7%), stomatitis (19.6%), and fatigue (17.4%). The overall response rate was 60.9%, 43.5% achieved a complete remission (CR), and 17.4% achieved CR with incomplete count recovery. The event-free survival at 1-year was 78.3%. Panobinostat in combination with idarubicin and cytarabine demonstrated tolerable safety and efficacy in younger patients with high-risk AML. The recommended phase 2 dose of panobinostat in this combination was 20 mg.
Filiaciones:
DeAngelo, DJ:
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
Walker, AR:
Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA
Schlenk, RF:
Natl Ctr Tumor Dis, NCT Trial Ctr, Heidelberg, Germany
Sierra, J:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Autonomous Univ Barcelona, Jose Carreras Inst, Barcelona, Spain
Medeiros, BC:
Stanford Univ, Sch Med, Stanford, CA 94305 USA
Ocio, EM:
Hosp Univ Salamanca, Salamanca IBSAL, Salamanca, Spain
CSIC, IBMCC, Ctr Invest Canc, Salamanca, Spain
Rollig, C:
Univ Klinikum Carl Gustav Carvus, Dresden, Germany
Strickland, SA:
Vanderbilt Ingram Canc Ctr, Nashville, TN USA
Thol, F:
Kliniken Med Hsch Hannover, Hannover, Germany
Valera, SZ:
Novartis Pharmaceut, E Hanover, NJ USA
Dasgupta, K:
Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India
Berkowitz, N:
Novartis Pharmaceut, E Hanover, NJ USA
Stuart, RK:
Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC USA
Green Accepted
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