title: Phase II randomized trial of carboplatin and gemcitabine with or without dexamethasone pre-treatment in patients with Stage IV non-small cell lung cancer.
abstract: OBJECTIVE
  Pre-clinical and early-phase clinical studies have demonstrated that dexamethasone (DEX) administration prior to chemotherapy reduces toxicity and enhances efficacy in the treatment of cancer. We undertook a randomized, phase II multi-institutional trial to evaluate these effects in patients with Stage IV non-small cell lung cancer.
  
  
  METHODS
  Patients were treated with carboplatin on day 1 and gemcitabine on days 1 and 8 every 21 days, for up to 6 cycles. Patients were randomized not to receive (Arm 1, n = 25) or to receive (Arm 2, n = 31) DEX orally for 4 days prior to chemotherapy on days 1 and 8. The primary endpoint was the incidence/course of grade 3 and 4 hematologic toxicity. Secondary endpoints included efficacy [response and overall survival (OS)] and evaluation of the Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, to predict survival and toxicity.
  
  
  RESULTS
  The incidence/course of grade 3 and 4 hematologic toxicity was significantly reduced in Arm 2 (DEX) versus Arm 1 (no DEX): neutrophils = 13 versus 40 % (p = 0.009) and platelets = 23 versus 44 % (p = 0.03). Response rates and OS were higher in Arm 2 versus Arm 1: 8/31 versus 2/25 (partial response, p = ns) and 378 versus 291 days (p = ns). The GPS significantly predicted survival OS (p = 0.04) but not toxicity.
  
  
  CONCLUSIONS
  Pre-treating patients with DEX is a safe, effective, and economic method of reducing the hematologic toxicity of carboplatin and gemcitabine. Our data suggest efficacy may also be enhanced by DEX pre-treatment.
authors.affiliation: Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA. john.rinehart@uky.edu
authors.forename: John
authors.initials: J
authors.lastname: Rinehart
authors.forename: Susanne
authors.initials: S
authors.lastname: Arnold
authors.forename: Goetz
authors.initials: G
authors.lastname: Kloecker
authors.forename: Allen
authors.initials: A
authors.lastname: Lim
authors.forename: Muhammad-Ali
authors.initials: MA
authors.lastname: Zaydan
authors.forename: Thomas
authors.initials: T
authors.lastname: Baeker
authors.forename: Jewraj G
authors.initials: JG
authors.lastname: Maheshwari
authors.forename: Harry
authors.initials: H
authors.lastname: Carloss
authors.forename: Stacey
authors.initials: S
authors.lastname: Slone
authors.forename: Brent
authors.initials: B
authors.lastname: Shelton
authors.forename: Jessica
authors.initials: J
authors.lastname: Croley
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kvale
authors.forename: Michael
authors.initials: M
authors.lastname: Brooks
authors.forename: Mark
authors.initials: M
authors.lastname: Leggas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012709:Serum Albumin / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D012709:Serum Albumin; D003841:Deoxycytidine; D003907:Dexamethasone; D002097:C-Reactive Protein; D016190:Carboplatin; D000093542:Gemcitabine