title: Combination of vorinostat and low dose cytarabine for patients with azacitidine-refractory/relapsed high risk myelodysplastic syndromes.
abstract: Outcome of patients with myelodysplastic syndrome after azacitidine failure is poor. In this population, we combined cytarabine (10-20mg/m²/day 14 days) with vorinostat (400mg/day) for escalating durations (7 days, 10 days and 14 days), and starting on day 1 (concomitant arm) or on day 14 (sequential arm) following a 3+3 phase I design. 40 patients were treated. Dose limiting toxicities were all seen in sequential arm. The overall response rate was 15% with 4 responses in concomitant arm (ORR=25%). We conclude that this combination is tolerable and concomitant administration might be less toxic and have better therapeutic effect (clinicaltrials.gov NCT00776503).
authors: Hematology Department, Institut PAOLI-CALMETTES and Aix-Marseille Université, Marseille, France.
authors: Thomas
authors: T
authors: Prebet
authors: Hematology Department, Hôpital Avicenne, Assistance Publique Hopitaux de Paris (AP-HP), Bobigny, France.
authors: Thorsten
authors: T
authors: Braun
authors: Hematology Department, Hôpital Purpan, Toulouse, France.
authors: Odile
authors: O
authors: Beyne-Rauzy
authors: Hematology Department, Hôpital Cochin, Assistance Publique Hopitaux de Paris (AP-HP), Paris, France.
authors: Francois
authors: F
authors: Dreyfus
authors: Hematology Department, Centre Henri Becquerel, Rouen, France.
authors: Aspasia
authors: A
authors: Stammatoullas
authors: Hematology Department, Hôpital Lyon Sud, Pierre-Bénite, France.
authors: Eric
authors: E
authors: Wattel
authors: Hematology Department, Centre Hospitalo universitaire, Strasbourg, France.
authors: Shanti
authors: S
authors: Ame
authors: Hematology Department, Hôpital Saint Louis, Assistance Publique Hopitaux de Paris (AP-HP), Paris, France.
authors: Emmanuel
authors: E
authors: Raffoux
authors: Hematology Department, Centre Hospitalo universitaire, Nantes, France.
authors: Jacques
authors: J
authors: Delaunay
authors: Hematology Department, Institut PAOLI-CALMETTES and Aix-Marseille Université, Marseille, France.
authors: Aude
authors: A
authors: Charbonnier
authors: Hematology Department, Hôpital Avicenne, Assistance Publique Hopitaux de Paris (AP-HP), Bobigny, France.
authors: Lionel
authors: L
authors: Adès
authors: Hematology Department, Hôpital Avicenne, Assistance Publique Hopitaux de Paris (AP-HP), Bobigny, France.
authors: Pierre
authors: P
authors: Fenaux
authors: Hematology Department, Institut PAOLI-CALMETTES and Aix-Marseille Université, Marseille, France. Electronic address: veyn@ipc.unicancer.fr.
authors: Norbert
authors: N
authors: Vey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D066298:In Vitro Techniques; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D003561:Cytarabine; D000077337:Vorinostat; D001374:Azacitidine
keywords: Azacitidine failure; Epigenetic; HDAC; Myelodysplasia