title: Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.
abstract: High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy.
  
  
  
  We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk premalignancy. Patients were randomized to treatment with cetuximab 400mg/m(2) on week one followed by 250mg/m(2) on week 2-8 or observation, with the option for crossover to cetuximab therapy for patients originally randomized to the observation arm.
  
  
  
  Two of 19 enrolled patients did not complete therapy due to treatment toxicity. Analysis of 17 patients who completed the trial regimen show a trend toward a larger mean decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2) (P=0.082, one-sided exact Wilcoxon rank sum test). However, in the observation group, none of the 5 patients (0%) achieved complete resolution of dysplasia; while 4 of 12 (33.3%) cetuximab treated patients had no remaining dysplasia after therapy.
  
  
  
  Treatment of high risk premalignancy of the upper aerodigestive tract with cetuximab alone may result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients. These results warrant further investigation in larger studies with increased statistical power.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Khan
authors.affiliation: University of Illinois Cancer Center, Chicago, IL, USA.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Epstein
authors.affiliation: Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Shanthi
authors.initials: S
authors.lastname: Marur
authors.affiliation: Medical University of South Carolina, Charleston, SC, USA.
authors.forename: M Boyd
authors.initials: MB
authors.lastname: Gillespie
authors.affiliation: University of Illinois Cancer Center, Chicago, IL, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Feldman
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sciubba
authors.affiliation: University of Pittsburg Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ferris
authors.affiliation: University of Pittsburg Medical Center, Pittsburgh, PA, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.affiliation: University of Pittsburg Medical Center, Pittsburgh, PA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gibson
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Koch
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Tufano
authors.affiliation: Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: William
authors.initials: W
authors.lastname: Westra
authors.affiliation: Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Tsottles
authors.affiliation: Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ozawa
authors.affiliation: Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Chung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Milton J Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD, USA. Electronic address: jcalifano@ucsd.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007818:Laryngeal Diseases / Q000188:drug therapy*; D008297:Male; D009059:Mouth Diseases / Q000188:drug therapy*; D010608:Pharyngeal Diseases / Q000188:drug therapy*; D011230:Precancerous Conditions / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab
keywords: Head and neck cancer; Head and neck premalignancy; Oral dysplasia