title: A randomized Phase 2 study of pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in patients with completely resected stage IB or II Non-Small-Cell Lung Cancer.
abstract: OBJECTIVE
  We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC).
  
  
  METHODS
  Patients in this multicenter, open-label, parallel-group, non-comparative Phase 2 study were randomized (1:1) to pemetrexed (500 mg/m(2)) with either cisplatin (75 mg/m(2)) or carboplatin (AUC5) for 4 cycles of 21 days. The primary endpoint was treatment feasibility (defined as 4 cycles completed with no cycle delay >42 days and ≤2 dose reductions, with a median relative dose intensity (RDI) ≥95% [overall]; and no Grade ≥3 toxicities at the follow-up visit 30 days after last drug administration). Secondary objectives included overall survival (OS) and safety.
  
  
  RESULTS
  We randomized 122 patients and treated 118. 71.9% (46/64) of patients in pemetrexed+cisplatin and 88.9% (48/54) in pemetrexed+carboplatin completed 4 cycles (median RDI >97% for all compounds). Neither treatment met the pre-defined feasibility level >60% of patients: 59.4% (95% confidence interval [CI]: 46.4;71.5) pemetrexed+cisplatin; 50.0% (95%CI: 36.1;63.9) in pemetrexed+carboplatin. In a post-hoc analysis considering only safety, both regimens were feasible with 81.3% (95%CI: 69.5;89.9) in pemetrexed+cisplatin and 90.7% (95%CI: 79.7;96.9) in pemetrexed+carboplatin. OS rates for both groups were 82-83% after 3 years and 80-83% after 5 years. Treatment-related Grade ≥3 adverse events (mostly hematological) were experienced by approximately 30% of patients in each group.
  
  
  CONCLUSIONS
  Although the study did not meet the primary objective, both treatment groups demonstrated good safety-related feasibility and tolerability as adjuvant treatment in patients with completely resected Stage IB/II NSCLC.
authors.affiliation: Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1, Mannheim, Germany. Electronic address: gerald.schmid-bindert@medma.uni-heidelberg.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid-Bindert
authors.affiliation: Kliniken der Stadt Köln, Ostmerheimer Str. 200, Köln, Germany. Electronic address: engelriedelw@kliniken-koeln.de.
authors.forename: Walburga
authors.initials: W
authors.lastname: Engel-Riedel
authors.affiliation: LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Wöhrendamm 80, Großhansdorf, Germany. Electronic address: m.reck@lungenclinic.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Krankenhaus Martha-Maria Halle-Doelau, Roentgenstr. 1, Halle/Saale, Germany. Electronic address: wolfgang.schuette@martha-maria.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuette
authors.affiliation: Tumorgenetik Bonn-Kooperation für Tumordiagnostik, Maximilianstrasse 28d, Bonn, Germany. Electronic address: info@individuelle-krebsberatung.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Stöhlmacher
authors.affiliation: Klinik Löwenstein, Geisshölzle 62, Löwenstein, Germany. Electronic address: jr.fischer@klinik-loewenstein.de.
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Fischer
authors.affiliation: Toulouse Universitary Hospital, Service de Pneumologie, Chemin De Pouvourville, Toulouse, France. Electronic address: mazieres.j@chu-toulouse.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.affiliation: Centre hospitalier Intercommunal de Créteil, 40 avenue de verdun, Créteil, France. Electronic address: christos.chouaid@chicreteil.fr.
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.affiliation: Klinikum Kassel, Mönchebergstr. 41-43, Kassel, Germany. Electronic address: mwolf@klinikum-kassel.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Hospital Clinic I Provinicial, Villarroel 170, Barcelona, Spain. Electronic address: nvinolas@clinic.ub.es.
authors.forename: Nuria
authors.initials: N
authors.lastname: Vinolas
authors.affiliation: Lilly Deutschland, Werner-Reimers-Straße 2-4, Bad Homburg, Germany. Electronic address: soldatenkova_victoria_vs@lilly.com.
authors.forename: Victoria
authors.initials: V
authors.lastname: Soldatenkova
authors.affiliation: Lilly France, 24 boulevard Vital Bouhot CS 50004, Neuilly-sur-Seine Cedex, France. Electronic address: v.ripoche@lilly.com.
authors.forename: Veronique
authors.initials: V
authors.lastname: Ripoche
authors.affiliation: Eli Lilly and Company,Lilly Corporate Center, Indianapolis, USA. Electronic address: guyen_tuan_stevon@lilly.co.
authors.forename: Tuan
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Lilly Oncology Europe, Grootslag 1-5, Houten, the Netherlands. Electronic address: cvg@lilly.com.
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D016190:Carboplatin; D002945:Cisplatin
keywords: Adjuvant treatment; Feasibility; NSCLC; Pemetrexed