title: Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.
abstract: OBJECTIVE
  To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy.
  
  
  RESULTS
  Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033).
  
  
  CONCLUSIONS
  Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.
authors.affiliation: Chest Disease Department, J. Minjoz University Hospital, 25030 Besançon Cedex, France. pneumo-depierre@ufc-chu.univ-fcomte.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Depierre
authors.forename: Bernard
authors.initials: B
authors.lastname: Milleron
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Bernard
authors.initials: B
authors.lastname: Lebeau
authors.forename: Denis
authors.initials: D
authors.lastname: Braun
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Breton
authors.forename: Etienne
authors.initials: E
authors.lastname: Lemarié
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gouva
authors.forename: Nadine
authors.initials: N
authors.lastname: Paillot
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Bréchot
authors.forename: Henri
authors.initials: H
authors.lastname: Janicot
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Lebas
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrioux
authors.forename: Jean
authors.initials: J
authors.lastname: Clavier
authors.forename: Pascal
authors.initials: P
authors.lastname: Foucher
authors.forename: Michel
authors.initials: M
authors.lastname: Monchâtre
authors.forename: Daniel
authors.initials: D
authors.lastname: Coëtmeur
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Level
authors.forename: Pascal
authors.initials: P
authors.lastname: Leclerc
authors.forename: François
authors.initials: F
authors.lastname: Blanchon
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rodier
authors.forename: Luc
authors.initials: L
authors.lastname: Thiberville
authors.forename: Anne
authors.initials: A
authors.lastname: Villeneuve
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.forename: Claude
authors.initials: C
authors.lastname: Chastang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011300:Preoperative Care; D016016:Proportional Hazards Models; D015996:Survival Rate
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide