title: Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study.
abstract: This phase Ib/II trial combined the pan-deacetylase inhibitor panobinostat with chemotherapy followed by panobinostat maintenance in elderly patients with newly diagnosed acute myeloid leukemia. Patients with prior history of myelodysplastic syndrome were excluded and 38 evaluable patients were included in the study (median age: 71 years; range: 65-83). Study patients received an induction with idarubicin (8 mg/m(2) iv days 1-3) plus cytarabine (100 mg/m(2) iv days 1-7) plus panobinostat po at escalating doses (days 8, 10, 12, 15, 17 and 19) that could be repeated in non-responding patients. Patients achieving complete remission received a consolidation cycle with the same schema, followed by panobinostat maintenance (40 mg po 3 days/week) every other week until progression. Thirty-one patients were treated at the maximum tolerated dose of panobinostat in the combination (10 mg) with good tolerability. Complete remission rate was 64% with a time to relapse of 17.0 months (12.8-21.1). Median overall survival for the whole series was 17 months (5.5-28.4). Moreover, in 4 of 5 patients with persistent minimal residual disease before maintenance, panobinostat monotherapy reduced its levels, with complete negativization in two of them. Maintenance phase was well tolerated. The most frequent adverse events were thrombocytopenia (25% grades 3/4), and gastrointestinal toxicity, asthenia and anorexia (mainly grades 1/2). Five patients required dose reduction during this phase, but only one discontinued therapy due to toxicity. These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and suggest further investigation is warranted, particularly in the context of maintenance therapy. This trial is registered at clinicaltrials.gov identifier: 00840346.
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca emocio@usal.es.
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ocio
authors.affiliation: Hospital Ramón y Cajal, Madrid.
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrera
authors.affiliation: Hospital Lozano Blesa, Zaragoza.
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Olave
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid.
authors.forename: Nerea
authors.initials: N
authors.lastname: Castro
authors.affiliation: Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Seville.
authors.forename: José A
authors.initials: JA
authors.lastname: Pérez-Simón
authors.affiliation: Hospital de la Santa Creu y Sant Pau, Barcelona.
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Hospital Germans Trias i Pujol, Badalona.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital San Carlos, Madrid.
authors.forename: Marta
authors.initials: M
authors.lastname: Mateo
authors.affiliation: Hospital Universitario La Fe, Valencia.
authors.forename: Miguel-Ángel
authors.initials: MÁ
authors.lastname: Sanz
authors.affiliation: Hospital Ramón y Cajal, Madrid.
authors.forename: Javier
authors.initials: J
authors.lastname: López
authors.affiliation: Hospital Universitario La Fe, Valencia.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: María-Carmen
authors.initials: MC
authors.lastname: Chillón
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Prieto-Conde
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: María
authors.initials: M
authors.lastname: Díez-Campelo
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Complejo Asistencial Universitario de Salamanca (IBSAL), Centro Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca.
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Clínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), IDISNA, Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D015255:Idarubicin / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D018365:Neoplasm, Residual; D000077767:Panobinostat; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D003561:Cytarabine; D000077767:Panobinostat; D015255:Idarubicin