Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy

Charles C.L. Tong, K. H.Vincent Lau, Michael Rivera, David Cannan, Julio Aguirre-Ghiso, Andrew G. Sikora, Vishal Gupta, Kevin Forsythe, Eric C. Ko, Krzysztof Misiukiewicz, Vivek Gurudutt, Marita S. Teng, Stuart H. Packer, Eric M. Genden, Johnny Kao

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5 Scopus citations


A phase II trial was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Patients with stage IVA-IVB or high-risk stage III squamous cell carcinomas were enrolled. Prior organ-conserving surgery or induction chemotherapy was allowed. IMRT was administered in 1.5 Gy fractions twice daily on days 1-5 of weeks 1, 3, 5, 7 ± 9 for a total dose of 60-73.5 Gy. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m 2). p16 INK4A expression was assessed by immunohistochemistry. From January 2007 to January 2010, 65 patients (61 with stage IV disease; 31 with oropharyngeal primaries) were enrolled. At a median follow-up of 28 months, 2-year locoregional control, distant control, progression-free survival, event-free survival and overall survival were 79, 83, 72, 63 and 80%, respectively. In 48 patients with available pre-treatment tissue, p16 overexpression was associated with significantly increased distant control (p=0.03), progression-free survival (p=0.02), event-free survival (p=0.007) and overall survival (p=0.03). The most common grade 3-4 toxicities were mucositis (46%), leukopenia (18%), anemia (18%) and dermatitis (17%). Concurrent 5-FU, HU, cetuximab and SIB-IMRT is a highly active regimen, particularly in patients with p16-positive disease.

Original languageEnglish (US)
Pages (from-to)1580-1586
Number of pages7
JournalOncology reports
Issue number5
Publication statusPublished - May 1 2012



  • Cetuximab
  • Chemoradiation
  • Epidermal growth factor receptor
  • Head and neck cancer
  • Intensity modulated radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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