title: Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer.
abstract: OBJECTIVE
  We incorporated cetuximab, a chimeric monoclonal antibody against the epidermal growth factor receptor (EGFR), into the induction therapy and subsequent chemoradiotherapy of head and neck cancer (HNC).
  
  
  METHODS
  Patients with locally advanced HNC, including squamous and undifferentiated histologies, were treated with docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and cetuximab 250 mg/m2 days 1, 8, and 15 (after an initial loading dose of 400 mg/m2), termed TPE, repeated every 21 days for three cycles, followed by radiotherapy with concurrent cisplatin 30 mg/m2 and cetuximab weekly (XPE), and maintenance cetuximab for 6 months. Quality of life (QOL) was assessed using Functional Assessment of Cancer Therapy-Head and Neck. In situ hybridization (ISH) for human papillomavirus (HPV), immunohistochemistry for p16, and fluorescence ISH for EGFR gene copy number were performed on tissue microarrays.
  
  
  RESULTS
  Of 39 enrolled patients, 36 had stage IV disease and 23 an oropharyngeal primary. Acute toxicities during TPE included neutropenic fever (10%) and during XPE, grade 3 or 4 oral mucositis (54%) and hypomagnesemia (39%). With a median follow-up of 36 months, 3-year progression-free survival and overall survival were 70% and 74%, respectively. Eight patients progressed in locoregional sites, three in distant, and one in both. HPV positivity was not associated with treatment efficacy. No progression-free patient remained G-tube dependent. The H&N subscale QOL scores showed a significant decrement at 3 months after XPE, which normalized at 1 year.
  
  
  CONCLUSIONS
  This cetuximab-containing regimen resulted in excellent long-term survival and safety, and warrants further evaluation in both HPV-positive and -negative HNC.
authors.affiliation: University of Pittsburgh Medical Center Cancer Pavilion, 5th Floor, Pittsburgh, PA 15232, USA. argirisae@upmc.edu
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Heron
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Smith
authors.forename: Seungwon
authors.initials: S
authors.lastname: Kim
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gibson
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Lai
authors.forename: Barton F
authors.initials: BF
authors.lastname: Branstetter
authors.forename: Donna M
authors.initials: DM
authors.lastname: Posluszny
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Johnson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin