title: A phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer: a study of the PMH phase II consortium.
abstract: BACKGROUND
  GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase II dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and >or=1 prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days.
  
  
  RESULTS
  Twenty-nine patients were treated, (24 NSCLC, 3 hormone-refractory prostate cancer, 1 head and neck, and 1 small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m(2) intravenously every 21days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase I, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D.
  
  
  CONCLUSIONS
  Activity of the combination at RP2D, GTI-2040 5 mg/kg/d x 14 days by CVI plus docetaxel 75 mg/m(2) does not seem superior to docetaxel alone in previously treated NSCLC.
authors.affiliation: Princess Margaret Hospital Phase 2 Consortium, Ontario, Canada. Natasha.Leighl@uhn.on.ca
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.forename: Xueyu E
authors.initials: XE
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Ellis
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Glenwood
authors.initials: G
authors.lastname: Goss
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Burkes
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Christopher
authors.initials: C
authors.lastname: Dick
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: James A
authors.initials: JA
authors.lastname: Zwiebel
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D009838:Oligodeoxyribonucleotides; D043823:Taxoids; D000077143:Docetaxel; C464617:GTI2040
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