title: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.
abstract: OBJECTIVE
  Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.
  
  
  METHODS
  This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles.
  
  
  RESULTS
  Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P <or= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.
  
  
  CONCLUSIONS
  In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.
authors.affiliation: University of Torino, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole, 10, Orbassano (Torino), Italy. giorgio.scagliotti@unito.it
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Purvish
authors.initials: P
authors.lastname: Parikh
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Bonne
authors.initials: B
authors.lastname: Biesma
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
authors.forename: Piotr
authors.initials: P
authors.lastname: Serwatowski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gatzemeier
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.forename: Mauro
authors.initials: M
authors.lastname: Zukin
authors.forename: Jin S
authors.initials: JS
authors.lastname: Lee
authors.forename: Anders
authors.initials: A
authors.lastname: Mellemgaard
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Shehkar
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: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Lorinda
authors.initials: L
authors.lastname: Simms
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Sugarman
authors.forename: David
authors.initials: D
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; 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; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine