title: Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: final results of a randomized, double-blind, placebo-controlled, phase 3 study.
abstract: BACKGROUND
  Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN.
  
  
  METHODS
  In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m(2) ) plus cisplatin (75 mg/m(2) ; n = 398) or placebo plus cisplatin (75 mg/m(2) ; n = 397) to assess overall survival (OS) and secondary endpoints.
  
  
  RESULTS
  Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors.
  
  
  CONCLUSIONS
  Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers.
authors.affiliation: Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA. surba@umich.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Urba
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
authors.forename: Tarini Prasad
authors.initials: TP
authors.lastname: Sahoo
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.forename: Klara
authors.initials: K
authors.lastname: Mezei
authors.forename: Christoph
authors.initials: C
authors.lastname: Reuter
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hitt
authors.forename: Francesca
authors.initials: F
authors.lastname: Russo
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Chang
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Hossain
authors.forename: Bente
authors.initials: B
authors.lastname: Frimodt-Moller
authors.forename: Andrew
authors.initials: A
authors.lastname: Koustenis
authors.forename: Ruey-Long
authors.initials: RL
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology*; D002945:Cisplatin / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D000068437:Pemetrexed; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin