title: Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaïve patients with advanced non-small cell lung cancer: a risk-benefit analysis of a large phase III study.
abstract: BACKGROUND
  In a large phase III study, cisplatin and pemetrexed had non-inferior efficacy and better tolerability compared with cisplatin and gemcitabine in chemonaïve patients with non-small cell lung cancer (NSCLC). The current analysis characterised the clinical benefit (i.e. survival) relative to clinical risk (i.e. drug-related toxicity) of the doublets.
  
  
  METHODS
  A total of 1669 patients (of 1725 randomised) received 500 mg/m(2) pemetrexed IV followed by 75 mg/m(2) cisplatin IV on day 1 or gemcitabine 1250 mg/m(2) on days 1 and 8 and 75 mg/m(2) cisplatin on day 1, administered every 3 weeks for up to 6 cycles. Survival without toxicity (i.e. clinical benefit to risk) was defined as the time from randomisation to the first occurrence of any grade 3 or 4 drug-related toxicity or death, and was analysed using Kaplan-Meier and Cox methods.
  
  
  RESULTS
  In the overall patient population, survival without grade 3 or 4 drug-related toxicity was significantly longer for patients treated with cisplatin and pemetrexed versus cisplatin and gemcitabine (HR=0.70; P<0.001), as was survival without grade 4 drug-related toxicity (HR=0.83; P<0.001). For patients with non-squamous NSCLC, survival without toxicity with cisplatin and pemetrexed was superior to cisplatin and gemcitabine for grade 3 or 4 drug-related toxicity (HR=0.64; P<0.001) and for grade 4 drug-related toxicity (HR=0.77; P<0.001), whereas no treatment-arm difference was observed in the squamous subgroup.
  
  
  CONCLUSIONS
  Patients with non-squamous NSCLC treated with front-line cisplatin and pemetrexed have superior survival without toxicity (i.e. clinical benefit-to-risk profile) compared with patients treated with cisplatin and gemcitabine.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, San Luigi Hospital, Regione Gonzole, 10 Orbassano, Torino 10043, Italy. scagliotti@ihnet.it
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Shekar
authors.initials: S
authors.lastname: Patil
authors.forename: Janusz
authors.initials: J
authors.lastname: Rolski
authors.forename: Tuncay
authors.initials: T
authors.lastname: Goksel
authors.forename: Renato
authors.initials: R
authors.lastname: Martins
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Gans
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.forename: Patrick
authors.initials: P
authors.lastname: Peterson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; 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* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D017410:Practice Guidelines as Topic; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine