title: Temporal changes in the efficacy of chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.
abstract: BACKGROUND
  Cytotoxic chemotherapy remains a standard treatment option for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN), but its effectiveness is debatable. We hypothesized palliative chemotherapy efficacy has decreased due to intensification of primary treatment, and investigated this by examining time trends of objective response rates (ORRs) in published reports of randomized trials (RCTs).
  
  
  METHODS
  RCTs with at least one arm studying chemotherapy alone in RMSCCHN patients and reporting ORR were identified and data extracted. Eligible regimens had at least 6 trial arms reporting ORR over 20 years. Weighted linear regressions of ORR by year of publication for eligible regimens were done, and predictors of ORR and survival were examined.
  
  
  RESULTS
  Three regimens were eligible for analysis: low dose methotrexate, single agent cisplatin, and cisplatin plus infusional 5-fluorouracil (PF). Linear regression showed decreasing ORRs over time for all three regimens studied: 23.5 to 9.8% (1980-2010) for methotrexate (p=0.06), 19.6 to 8.8% (1980-2010) for cisplatin (p=0.0013), and 37.6 to 27.9% (1990-2010) for PF (p=0.11). Trial sample size, oropharynx cancer primary site, use of PF, and prior treatment increased over time. Use of PF and year of publication were the strongest predictors of ORR.
  
  
  CONCLUSIONS
  These data confirm the limited effectiveness of currently available palliative chemotherapy regimens for RMSCCHN patients. Novel therapeutics offering improvements in quality and quantity of life are urgently needed for these patients. Based on these results, the study of such agents as first-line therapy in RMSCCHN patients is entirely justifiable.
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada. Electronic address: eric.winquist@lhsc.on.ca.
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
authors.forename: Intisar
authors.initials: I
authors.lastname: Al-Rasheedy
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada; Department of Otolaryngology/Head & Neck Surgery, Western University, London, Ontario, Canada.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Nichols
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Larry
authors.initials: L
authors.lastname: Stitt
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016014:Linear Models; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D008727:Methotrexate
keywords: Drug therapy; Head and neck neoplasms; Metastatic; Review