title: Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma.
abstract: OBJECTIVE
  We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.
  
  
  METHODS
  In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.
  
  
  RESULTS
  All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.
  
  
  CONCLUSIONS
  Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
authors.affiliation: City of Hope, Duarte, CA, USA. mkirschbaum@nvcancer.org
authors.forename: Mark
authors.initials: M
authors.lastname: Kirschbaum
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Leslie
authors.initials: L
authors.lastname: Popplewell
authors.forename: Jasmine
authors.initials: J
authors.lastname: Zain
authors.forename: Maria
authors.initials: M
authors.lastname: Delioukina
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Deron
authors.initials: D
authors.lastname: Matsuoka
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pulone
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Rotter
authors.forename: Igor
authors.initials: I
authors.lastname: Espinoza-Delgado
authors.forename: Auayporn
authors.initials: A
authors.lastname: Nademanee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: David
authors.initials: D
authors.lastname: Gandara
authors.forename: Edward
authors.initials: E
authors.lastname: Newman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat