title: Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC).
abstract: OBJECTIVE
  We previously reported inferior outcomes for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy (IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with IMRT for LAHNSCC.
  
  
  METHODS
  Retrospective review was performed for LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to 04/08 with concurrent cetuximab (n=49), 5FU/carboplatin (n=52), or cisplatin (n=259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant metastasis-free survival, and late toxicity were analyzed using univariate and multivariate analyses. OS analysis was confirmed by propensity score adjustment.
  
  
  RESULTS
  Treatment groups were similar with regard to primary tumor site, overall stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients were older, with lower performance status, more comorbidities, higher T classification, and worse renal function. On multivariate analysis, compared with cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS (86.9% vs. 70.2% vs. 40.9%; P<.0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%; P<.0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin (8.0%) vs. cetuximab (7.7%).
  
  
  CONCLUSIONS
  Although 5FU/carboplatin patients were sicker and experienced greater toxicity than cisplatin patients, no significant difference was found in all endpoints. In contrast, despite similar pretreatment characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly worse. We feel that caution should be used with routine use of cetuximab in the management of LAHNSCC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States.
authors.forename: Lauren Q
authors.initials: LQ
authors.lastname: Shapiro
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY, United States.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sherman
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Riaz
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Setton
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Koutcher
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY, United States.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY, United States.
authors.forename: Weiji
authors.initials: W
authors.lastname: Shi
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY, United States.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Fury
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Wolden
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Pfister
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY, United States.
authors.forename: Luc
authors.initials: L
authors.lastname: Morris
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, United States. Electronic address: leen2@mskcc.org.
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil