title: Three-Year Follow-Up of a Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (the TREAT Study).
abstract: BACKGROUND
  Adjuvant chemotherapy in non-small cell lung cancer (NSCLC) improves survival but is associated with significant toxicity. The Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (TREAT study) was designed to test the hypothesis that a protocol with reduced toxicity might improve feasibility of postoperative delivery of adjuvant chemotherapy drugs to patients with NSCLC, thereby improving compliance and, potentially, survival.
  
  
  METHODS
  Two adjuvant regimens were evaluated for feasibility in 132 patients with NSCLC: the standard regimen of cisplatin and vinorelbine (CVb) (cisplatin 50 mg/m(2) on day 1 and day 8 and vinorelbine 25 mg/m(2) on days 1, 8, 15, and 22 every 4 weeks) and a regimen consisting of cisplatin and pemetrexed (CPx) (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 every 3 weeks). The primary end-point analysis showing that CPx is safe and feasible with dose delivery superior to that of CVb has already been published. Here we report the 3-year follow-up results of the secondary efficacy end points-overall, relapse-free, distant metastasis-free, and local relapse-free survival-also with regard to histologic diagnosis.
  
  
  RESULTS
  After a median of 39 months, no significant differences in any of the outcome parameters between CVb and CPx were observed. Also, histologic diagnosis and tumor size in stage IB did not influence survival in the CPx-treated patients. Yet, Cox regression analyses showed that overall survival at 3 years was significantly correlated with feasibility and the occurrence of dose-limiting toxicity.
  
  
  CONCLUSIONS
  Although adjuvant chemotherapy with CPx is safe and characterized by less toxicity and better dose delivery than CVb, overall survival was not influenced by treatment arm in the context of this phase II trial.
authors.affiliation: Pneumology, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany. Electronic address: kreuter@uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.affiliation: Respiratory Oncology Unit (Pneumology Department), University Hospital KU Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.affiliation: Department of Internal Medicine II, Oncology, Klinik Loewenstein, Lowenstein, Germany.
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Fischer
authors.affiliation: Department of Medical Oncology, University Hospital Essen, West German Cancer Centre, Ruhrlandklinik, University of Duisburg-Essen, Germany.
authors.forename: Wilfried E
authors.initials: WE
authors.lastname: Eberhardt
authors.affiliation: Department of Thoracic Surgery, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Zabeck
authors.affiliation: Department of Pneumology, Lungenklinik Heckeshorn, HELIOS-Klinikum Emil von Behring, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kollmeier
authors.affiliation: Department of Pneumology III, Lungenklinik Hemer, Hemer, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Serke
authors.affiliation: Department of Hematology/Oncology, Dr.-Horst-Schmidt-Kliniken GmbH, Wiesbaden, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Frickhofen
authors.affiliation: Department of Thoracic Oncology, Lungen Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Lungenklinik Merheim, Kliniken der Stadt Köln, Cologne, Germany.
authors.forename: Walburga
authors.initials: W
authors.lastname: Engel-Riedel
authors.affiliation: Department of Hematology and Oncology, Georg-August-Universität, Göttingen, Germany and Interdisciplinary Center for Oncology, Wolfsburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Department of Respiratory Medicine Ziekenhuis Oost Limburg, Genk, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Thomeer
authors.affiliation: Department of Internal Medicine II, University Clinic Ulm, and Clinic for Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Kempten and Immenstadt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schumann
authors.affiliation: Department of Thoracic Surgery, Universities Hospital Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: De Leyn
authors.affiliation: Department of Thoracic Surgery, Klinik Loewenstein, Loewenstein, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Graeter
authors.affiliation: Department of Thoracic Surgery, Ruhrlandklinik Essen, University Hospital of University Duisburg-Essen, Essen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Stamatis
authors.affiliation: Department of Hematology and Oncology, Pius-Hospital Oldenburg, Oldenburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
authors.affiliation: Thoracic Oncology, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology*; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D013997:Time Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000068437:Pemetrexed; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Adjuvant chemotherapy; Non–small cell lung cancer; Outcome; Pemetrexed; Toxicity