title: Phase II study of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stage III non-small cell lung cancer.
abstract: BACKGROUND
  Pemetrexed has emerged as one of the most active agents for the treatment of patients with advanced non-small cell lung cancer (NSCLC). We conducted a phase II study to assess the efficacy and feasibility of integrating pemetrexed in a concurrent therapy plan for patients with stage III NSCLC.
  
  
  METHODS
  Patients with stage III NSCLC with performance status 0 to 1, adequate organ function including pulmonary function, and V20 less than 40% were eligible. Patients were treated with cisplatin 75 mg/m² (first five patients 60 mg/m²) and pemetrexed 500 mg/m² every 21 days for three cycles with chest radiotherapy to 66 Gy. Patients then received three cycles of docetaxel 75 mg/m² every 21 days. Tumors were analyzed for Excision Repair Cross Complementation Group 1 and thymidylate synthase.
  
  
  RESULTS
  Patient characteristics (N = 28) were median age, 60; males, 68%; stage IIIB, 64%; and squamous cell, 43%. Twenty-four patients (86%) completed all three cycles of cisplatin/pemetrexed. Of the 24 patients eligible for docetaxel, 21 (87%) received it. Grade 3/4 toxicities were neutropenia (39%), febrile neutropenia (14%), esophagitis (14%), and pneumonitis (4%). Median survival was 34 months, and 1-year survival was 66%. Survival was not significantly different in squamous and other histology patients. Tumor analysis in 16 patients showed that moderate/strong expression of thymidylate synthase was significantly associated with progression-free survival and overall survival.
  
  
  CONCLUSIONS
  Integrating pemetrexed in a concurrent therapy regimen for patients with stage III NSCLC is feasible and was associated with a median survival of 34 months.
authors.affiliation: Thoracic Oncology Program, Karmanos Cancer Institute/Wayne State University, Detroit, Michigan, USA. gadgeels@karmanos.org
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.forename: John C
authors.initials: JC
authors.lastname: Ruckdeschel
authors.forename: Bhaumik B
authors.initials: BB
authors.lastname: Patel
authors.forename: Antoinette
authors.initials: A
authors.lastname: Wozniak
authors.forename: Andre
authors.initials: A
authors.lastname: Konski
authors.forename: Manuel
authors.initials: M
authors.lastname: Valdivieso
authors.forename: Deborah
authors.initials: D
authors.lastname: Hackstock
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Kimberly
authors.initials: K
authors.lastname: Belzer
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Burger
authors.forename: Lauren
authors.initials: L
authors.lastname: Marquette
authors.forename: Andrew
authors.initials: A
authors.lastname: Turrisi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism; D000077143:Docetaxel; D004720:Endonucleases / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D009367:Neoplasm Staging; D000068437:Pemetrexed; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin