title: Phase I trial of radiation with concurrent and consolidation pemetrexed and cisplatin in patients with unresectable stage IIIA/B non-small-cell lung cancer.
abstract: OBJECTIVE
  To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy.
  
  
  RESULTS
  Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%.
  
  
  CONCLUSIONS
  Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada. anthony.brade@rmp.uhn.on.ca
authors.forename: Anthony
authors.initials: A
authors.lastname: Brade
authors.forename: Andrea
authors.initials: A
authors.lastname: Bezjak
authors.forename: Robert
authors.initials: R
authors.lastname: MacRae
authors.forename: Scott
authors.initials: S
authors.lastname: Laurie
authors.forename: Alex
authors.initials: A
authors.lastname: Sun
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
authors.forename: Shannon
authors.initials: S
authors.lastname: Pearson
authors.forename: Bernadette
authors.initials: B
authors.lastname: Southwood
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Shauna
authors.initials: S
authors.lastname: McGill
authors.forename: Neill
authors.initials: N
authors.lastname: Iscoe
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin