title: Results of a phase II study of vorinostat in combination with intravenous fludarabine, mitoxantrone, and dexamethasone in patients with relapsed or refractory mantle cell lymphoma: an interim analysis.
abstract: OBJECTIVE
  Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL.
  
  
  METHODS
  The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles.
  
  
  RESULTS
  Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction.
  
  
  CONCLUSIONS
  V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy.
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Korea University College of Medical College, Seoul, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Republic of Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kong
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea.
authors.forename: Byung-Su
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Won
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Medical College, Bucheon, Republic of Korea.
authors.forename: Sung-Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul, 135-710, Republic of Korea. wskimsmc@skku.edu.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D007262:Infusions, Intravenous; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011788:Quality of Life; D012008:Recurrence; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat; D003907:Dexamethasone; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine
keywords: Mantle cell lymphoma; Phase II; Relapsed lymphoma; Vorinostat