title: Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).
abstract: BACKGROUND
  Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations.
  
  
  METHODS
  Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles.
  
  
  RESULTS
  A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens.
  
  
  CONCLUSIONS
  Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.
authors.affiliation: Department of Medical Oncology, National Tumor Institute, Naples, Italy. pasqualecomella@libero.it
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: G
authors.initials: G
authors.lastname: Filippelli
authors.forename: G
authors.initials: G
authors.lastname: De Cataldis
authors.forename: B
authors.initials: B
authors.lastname: Massidda
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: L
authors.initials: L
authors.lastname: Maiorino
authors.forename: C
authors.initials: C
authors.lastname: Putzu
authors.forename: S
authors.initials: S
authors.lastname: Mancarella
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: R
authors.initials: R
authors.lastname: Cioffi
authors.forename: M
authors.initials: M
authors.lastname: Roselli
authors.forename: F
authors.initials: F
authors.lastname: Buzzi
authors.forename: V
authors.initials: V
authors.lastname: Milia
authors.forename: A
authors.initials: A
authors.lastname: Gambardella
authors.forename: D
authors.initials: D
authors.lastname: Natale
authors.forename: M
authors.initials: M
authors.lastname: Bianco
authors.forename: M
authors.initials: M
authors.lastname: Ghiani
authors.forename: P
authors.initials: P
authors.lastname: Masullo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine; D000093542:Gemcitabine