title: Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST).
abstract: BACKGROUND
  The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G).
  
  
  METHODS
  A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets.
  
  
  RESULTS
  For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens.
  
  
  CONCLUSIONS
  This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.
authors.affiliation: Oncology Unit, S Maria Nuova Hospital, Viale Risorgimento 80, Reggio Emilia 42123, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Boni
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
authors.forename: L
authors.initials: L
authors.lastname: Boni
authors.forename: E
authors.initials: E
authors.lastname: Baldini
authors.forename: F
authors.initials: F
authors.lastname: Recchia
authors.forename: C
authors.initials: C
authors.lastname: Barone
authors.forename: F
authors.initials: F
authors.lastname: Grossi
authors.forename: D
authors.initials: D
authors.lastname: Germano
authors.forename: E
authors.initials: E
authors.lastname: Matano
authors.forename: G
authors.initials: G
authors.lastname: Marini
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.forename: F
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: A
authors.initials: A
authors.lastname: Bagnulo
authors.forename: C
authors.initials: C
authors.lastname: Pennucci
authors.forename: C
authors.initials: C
authors.lastname: Caroti
authors.forename: M
authors.initials: M
authors.lastname: Mencoboni
authors.forename: F
authors.initials: F
authors.lastname: Zanelli
authors.forename: T
authors.initials: T
authors.lastname: Prochilo
authors.forename: M A
authors.initials: MA
authors.lastname: Cafferata
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide; D000093542:Gemcitabine