title: Randomized phase 2 sequencing and pharmacokinetic study of gemcitabine and oxaliplatin in advanced non-small cell lung cancer.
abstract: OBJECTIVE
  This multicentre phase II trial examined the combination of gemcitabine and oxaliplatin in patients with advanced non-small cell lung cancer (NSCLC). The effect of sequence administration was randomized and pharmacokinetics (PK) assessed.
  
  
  METHODS
  Eligible patients had stage IIIB or IV or recurrent NSCLC, no prior chemotherapy, World Health Organization performance status ≤2 and measurable disease. Treatment comprised: gemcitabine (1250 mg/m(2)) and oxaliplatin (70 mg/m(2)), each given on days 1 and 8 of a 21-day cycle. Patients were randomized 1:1 to the sequencing of the two drugs for the duration of their treatment. The primary end-point was response rate (RR). Secondary end-points included progression-free survival (PFS), overall survival (OS), toxicity, PK and the effect of drug sequencing.
  
  
  RESULTS
  A total of 46 patients were enrolled of whom 43 were evaluable for response. Overall 13 patients (30%) achieved a partial response, PFS was 4.2 months (95% CI 2.8-5.8 months), and OS was 6.8 months (95% CI 4.4-10.1 months). There was only one case of grade 3 neurosensory toxicity despite a median cumulative oxaliplatin dose in excess of 500 mg/m(2) . No differences in clinical or PK end-points were observed between the two different sequencing arms.
  
  
  CONCLUSIONS
  This oxaliplatin and gemcitabine schedule has shown activity in advanced NSCLC with modest toxicity. Neither clinical nor PK outcomes were influenced by the sequencing of these agents, although definite conclusions are limited by small patient numbers. The favorable toxicity profile of this doublet, in light of an encouraging RR, warrants its further investigation in NSCLC.
authors.affiliation: Department of Medical Oncology, Austin Hospital, Queensland, Australia. paul.mitchell@austin.org.au
authors.forename: Paul L
authors.initials: PL
authors.lastname: Mitchell
authors.forename: Adam
authors.initials: A
authors.lastname: Broad
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosenthal
authors.forename: Peter
authors.initials: P
authors.lastname: Galettis
authors.forename: Rick
authors.initials: R
authors.lastname: Abraham
authors.forename: Ivon
authors.initials: I
authors.lastname: Burns
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.forename: Alvin
authors.initials: A
authors.lastname: Milner
authors.forename: Juliana
authors.initials: J
authors.lastname: Diiulio
authors.forename: Matthew
authors.initials: M
authors.lastname: Links
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine