title: Trial on refinement of early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: the TREAT protocol.
abstract: BACKGROUND
  Adjuvant chemotherapy has been proven to be beneficial for patients with early stage non-small cell lung cancer. However, toxicity and insufficient dose delivery have been critical issues with the chemotherapy used. Doublet regimens with pemetrexed, a multi-target folate inhibitor, and platin show clear activity in non-small cell lung cancer and are well tolerated with low toxicity rates and excellent delivery.
  
  
  METHODS
  In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms.
  
  
  CONCLUSIONS
  The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival.
authors.affiliation: Department of Medicine/Thoracic Oncology, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany. michael.kreuter@thoraxklinik-heidelberg.de <michael.kreuter@thoraxklinik-heidelberg.de>
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Paul
authors.initials: P
authors.lastname: De Leyn
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
mesh_terms: D024221:Antineoplastic Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D000068437:Pemetrexed; D011446:Prospective Studies; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D014747:Vinblastine; D006147:Guanine; D002945:Cisplatin; D000077235:Vinorelbine