title: A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial).
abstract: OBJECTIVE
  There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases.
  
  
  RESULTS
  A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed.
  
  
  CONCLUSIONS
  This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.
authors.affiliation: Centre Hospitalier Régional Universitaire de Besançon, Université de Franche-Comté, EA 3181, France. virginie.westeel@univ-fcomte.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Marc
authors.initials: M
authors.lastname: Puyraveau
authors.forename: A
authors.initials: A
authors.lastname: Lavolé
authors.forename: Denis
authors.initials: D
authors.lastname: Braun
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
authors.forename: Laurence
authors.initials: L
authors.lastname: Bigay-Game
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Gervais
authors.initials: G
authors.lastname: Ozenne
authors.forename: Alain
authors.initials: A
authors.lastname: Rivière
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Bernard
authors.initials: B
authors.lastname: Lebeau
authors.forename: Didier
authors.initials: D
authors.lastname: Debieuvre
authors.forename: Michel
authors.initials: M
authors.lastname: Poudenx
authors.forename: Philippe
authors.initials: P
authors.lastname: David
authors.forename: Olivier
authors.initials: O
authors.lastname: Molinier
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Etienne
authors.initials: E
authors.lastname: Lemarié
authors.forename: Franck
authors.initials: F
authors.lastname: Morin
authors.forename: Alain
authors.initials: A
authors.lastname: Depierre
authors.forename: Bernard
authors.initials: B
authors.lastname: Milleron
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D019990:Perioperative Care; D011300:Preoperative Care; D011788:Quality of Life; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Adjuvant chemotherapy; Early-stage; Neo-adjuvant chemotherapy; Non-small-cell lung cancer; Randomised trial