title: Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer.
abstract: Treatment intensification for resected, high-risk, head and neck squamous cell carcinoma (HNSCC) is an area of active investigation with novel adjuvant regimens under study. In this trial, the epidermal growth-factor receptor (EGFR) pathway was targeted using the IgG2 monoclonal antibody panitumumab in combination with cisplatin chemoradiotherapy (CRT) in high-risk, resected HNSCC.
  
  
  
  Eligible patients included resected pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV)-negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1 mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes). Postoperative treatment consisted of standard RT (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m2and weekly panitumumab 2.5 mg/kg. The primary endpoint was progression-free survival (PFS).
  
  
  
  Forty-six patients were accrued; 44 were evaluable and were analyzed. The median follow-up for patients without recurrence was 49 months (range 12-90 months). The probability of 2-year PFS was 70% (95% CI = 58%-85%), and the probability of 2-year OS was 72% (95% CI = 60%-87%). Fourteen patients developed recurrent disease, and 13 (30%) of them died. An additional five patients died from causes other than HNSCC. Severe (grade 3 or higher) toxicities occurred in 14 patients (32%).
  
  
  
  Intensification of adjuvant treatment adding panitumumab to cisplatin CRT is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative HNSCC patients. Further targeted monoclonal antibody combinations are warranted.
  
  
  
  NCT00798655.
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh ferrrl@upmc.edu.|Departments of Otolaryngology, Division of Head and Neck Surgery.|Immunology.
authors.forename: R L
authors.initials: RL
authors.lastname: Ferris
authors.affiliation: Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh.
authors.forename: J L
authors.initials: JL
authors.lastname: Geiger
authors.affiliation: Departments of Otolaryngology, Division of Head and Neck Surgery.
authors.forename: S
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Department of Otolaryngology, Johns Hopkins University, Baltimore.|Tumor Biology Section, National Institute of Deafness and Communication Disorders, National Institutes of Health, Bethesda.
authors.forename: N C
authors.initials: NC
authors.lastname: Schmitt
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh.|Departments of Otolaryngology, Division of Head and Neck Surgery.|Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Heron
authors.affiliation: Departments of Otolaryngology, Division of Head and Neck Surgery.
authors.forename: J T
authors.initials: JT
authors.lastname: Johnson
authors.affiliation: Departments of Otolaryngology, Division of Head and Neck Surgery.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Departments of Otolaryngology, Division of Head and Neck Surgery.
authors.forename: U
authors.initials: U
authors.lastname: Duvvuri
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh.|Department of Otolaryngology, Johns Hopkins University, Baltimore.
authors.forename: D A
authors.initials: DA
authors.lastname: Clump
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh.|Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh.
authors.forename: J E
authors.initials: JE
authors.lastname: Bauman
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh.|Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh.
authors.forename: J P
authors.initials: JP
authors.lastname: Ohr
authors.affiliation: Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh.
authors.forename: W E
authors.initials: WE
authors.lastname: Gooding
authors.affiliation: Department of Medical Oncology, Hygeia Hospital, Athens, Greece.|Department of Medical Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Argiris
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D000077544:Panitumumab; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin
keywords: cisplatin chemoradiotherapy; clinical trial; head and neck squamous cell carcinoma; panitumumab