title: Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-naïve patients with non-small-cell lung cancer.
  
  
  METHODS
  Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8.
  
  
  RESULTS
  One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms.
  
  
  CONCLUSIONS
  Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.
authors.affiliation: Department of Oncology and Medicine, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Cynthia X
authors.initials: CX
authors.lastname: Ma
authors.forename: Suresh
authors.initials: S
authors.lastname: Nair
authors.forename: Sachdev
authors.initials: S
authors.lastname: Thomas
authors.forename: Sumithra J
authors.initials: SJ
authors.lastname: Mandrekar
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
authors.forename: Harold E
authors.initials: HE
authors.lastname: Windschitl
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Hillman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine