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 Packer, Eric M. Genden, Johnny Kao

Research output: Contribution to journalArticle

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Abstract

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
Volume27
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Hydroxyurea
Head and Neck Neoplasms
Fluorouracil
Disease-Free Survival
Radiotherapy
Cyclin-Dependent Kinase Inhibitor p16
Mucositis
Induction Chemotherapy
Survival
Leukopenia
Dermatitis
Anemia
Squamous Cell Carcinoma
Immunohistochemistry
Cetuximab
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy. / Tong, Charles C L; Lau, K. H Vincent; Rivera, Michael; Cannan, David; Aguirre-Ghiso, Julio; Sikora, Andrew G.; Gupta, Vishal; Forsythe, Kevin; Ko, Eric C.; Misiukiewicz, Krzysztof; Gurudutt, Vivek; Teng, Marita S.; Packer, Stuart; Genden, Eric M.; Kao, Johnny.

In: Oncology Reports, Vol. 27, No. 5, 05.2012, p. 1580-1586.

Research output: Contribution to journalArticle

Tong, CCL, Lau, KHV, Rivera, M, Cannan, D, Aguirre-Ghiso, J, Sikora, AG, Gupta, V, Forsythe, K, Ko, EC, Misiukiewicz, K, Gurudutt, V, Teng, MS, Packer, S, Genden, EM & Kao, J 2012, 'Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy', Oncology Reports, vol. 27, no. 5, pp. 1580-1586. https://doi.org/10.3892/or.2012.1679
Tong, Charles C L ; Lau, K. H Vincent ; Rivera, Michael ; Cannan, David ; Aguirre-Ghiso, Julio ; Sikora, Andrew G. ; Gupta, Vishal ; Forsythe, Kevin ; Ko, Eric C. ; Misiukiewicz, Krzysztof ; Gurudutt, Vivek ; Teng, Marita S. ; Packer, Stuart ; Genden, Eric M. ; Kao, Johnny. / Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy. In: Oncology Reports. 2012 ; Vol. 27, No. 5. pp. 1580-1586.
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abstract = "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.",
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