title: Phase II study of the histone deacetylase inhibitor Romidepsin in relapsed small cell lung cancer (Cancer and Leukemia Group B 30304).
abstract: BACKGROUND
  Treatment of small cell lung cancer (SCLC) is initially gratifying with most patients responding to platinum-based chemotherapy. Treatment of relapsed disease gives much lower response rates of short duration. We undertook this study of the protein deacetylase inhibitor Romidepsin in chemosensitive recurrent SCLC based on preclinical data that suggested this to be an active target.
  
  
  METHODS
  Patients had recurrent chemosensitive SCLC (relapse ≥90 days since completion of platinum-based chemotherapy). Treatment was administered as weekly infusions of Romidepsin at 13 mg/m(2) for 3 of 4 weeks. We designed a two-stage phase II study targeting a response rate of 30% (<10% response would be uninteresting and ≥30% worthy of further study).
  
  
  RESULTS
  Sixteen patients (10 male, 6 female) were accrued to the first stage of this study. Most (11 patients, 69%) presented with extensive-stage SCLC, and all had received prior chemotherapy, with 11 having received prior radiation. Eastern Cooperative Oncology Group performance status was excellent with 0 in 6 patients (38%) and 1 in 10 patients. No objective responses were seen, and stable disease was the best response seen in 3 patients (19%). Toxicity was modest with 3 patients suffering grade 3 toxicity (lymphopenia, insomnia, nausea, vomiting, and hyponatremia) and one patient with grade 4 thrombocytopenia. Median progression-free survival was 1.8 months, and median overall survival was 6 months.
  
  
  CONCLUSIONS
  Romidepsin given on a weekly schedule in patients with chemosensitive, recurrent SCLC was inactive and will not be pursued further in this setting.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA. greg.otterson@osumc.edu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Lydia
authors.initials: L
authors.lastname: Hodgson
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D047630:Depsipeptides / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D016879:Salvage Therapy; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; C087123:romidepsin; D006655:Histone Deacetylases