title: Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.
abstract: BACKGROUND
  The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design.
  
  
  RESULTS
  Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy.
  
  
  CONCLUSIONS
  Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA, txh@medicine.wisc.edu.
authors.forename: Tien
authors.initials: T
authors.lastname: Hoang
authors.forename: Toby C
authors.initials: TC
authors.lastname: Campbell
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.forename: Kyungmann
authors.initials: K
authors.lastname: Kim
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kolesar
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Oettel
authors.forename: Jules H
authors.initials: JH
authors.lastname: Blank
authors.forename: Emily G
authors.initials: EG
authors.lastname: Robinson
authors.forename: Harish G
authors.initials: HG
authors.lastname: Ahuja
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Kirschling
authors.forename: Peter H
authors.initials: PH
authors.lastname: Johnson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Huie
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wims
authors.forename: Martha M
authors.initials: MM
authors.lastname: Larson
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Hernan
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D001897:Boronic Acids; D006877:Hydroxamic Acids; D011719:Pyrazines; D000077337:Vorinostat; D000069286:Bortezomib