title: Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study.
abstract: BACKGROUND
  Adjuvant chemotherapy is beneficial in non-small-cell lung cancer (NSCLC). However, balancing toxicity and efficacy mandates improvement.
  
  
  METHODS
  Patients with completely resected stages IB-pT3N1 NSCLC were randomly assigned to either four cycles cisplatin (C: 50 mg/m(2) day (d)1 + 8) and vinorelbine (V: 25 mg/m(2) d1, 8, 15, 22) q4 weeks or four cycles cisplatin (75 mg/m(2) d1) and pemetrexed (Px: 500 mg/m(2) d1) q3 weeks. Primary objective was the clinical feasibility rate (no grade (G)4 neutropenia/thrombocytopenia or thrombocytopenia with bleeding, no G3/4 febrile neutropenia or non-hematological toxicity; no premature withdrawal/death). Secondary objectives were drug delivery and efficacy.
  
  
  RESULTS
  One hundred and thirty two patients were randomized (stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous). The feasibility rates were 95.5% (cisplatin and pemetrexed, CPx) and 75.4% (cisplatin and vinorelbine, CVb) (P = 0.001); hematological G3/4 toxic effects were 10% (CPx) and 74% (CVb) (P < 0.001), non-hematological toxic effects were comparable (33% and 31%, P = 0.798). Delivery of total mean doses was 90% of planned with CPx, but 66% (cisplatin) and 64% (vinorelbine) with CVb (P < 0.0001). The median number of cycles [treatment time (weeks)] was 4 for CPx (11.2) and 3 for CVb (9.9). Time to withdrawal from therapy differed significantly between arms favoring CPx (P < 0.001).
  
  
  CONCLUSIONS
  Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared with CVb.
authors.affiliation: Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. michael.kreuter@thoraxklinik-heidelberg.de
authors.forename: M
authors.initials: M
authors.lastname: Kreuter
authors.forename: J
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: J R
authors.initials: JR
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Eberhardt
authors.forename: H
authors.initials: H
authors.lastname: Zabeck
authors.forename: J
authors.initials: J
authors.lastname: Kollmeier
authors.forename: M
authors.initials: M
authors.lastname: Serke
authors.forename: N
authors.initials: N
authors.lastname: Frickhofen
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.forename: W
authors.initials: W
authors.lastname: Engel-Riedel
authors.forename: S
authors.initials: S
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Thomeer
authors.forename: C
authors.initials: C
authors.lastname: Schumann
authors.forename: P
authors.initials: P
authors.lastname: De Leyn
authors.forename: T
authors.initials: T
authors.lastname: Graeter
authors.forename: G
authors.initials: G
authors.lastname: Stamatis
authors.forename: I
authors.initials: I
authors.lastname: Zuna
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: M
authors.initials: M
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D014747:Vinblastine; D006147:Guanine; D002945:Cisplatin; D000077235:Vinorelbine