Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer

Johnny Kao, Eric M. Genden, Vishal Gupta, Edelweiss L. Policarpio, Ryan J. Burri, Michael Rivera, Vivek Gurudutt, Peter M. Som, Marita Teng, Stuart Packer

Research output: Contribution to journalArticle

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Abstract

Background: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Method: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m 2), HU (500 mg twice daily), and cetuximab (250 mg/m2). Results: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≤4 adverse events. Conclusions: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.

Original languageEnglish (US)
Pages (from-to)318-326
Number of pages9
JournalCancer
Volume117
Issue number2
DOIs
StatePublished - Jan 15 2011
Externally publishedYes

Fingerprint

Hydroxyurea
Head and Neck Neoplasms
Fluorouracil
Radiotherapy
Radiodermatitis
Cetuximab
Mucositis
Induction Chemotherapy
Leukopenia
Enteral Nutrition
Therapeutics
Neutropenia
Disease-Free Survival
Anemia
Radiation

Keywords

  • cetuximab
  • chemoradiation
  • epidermal growth factor receptor
  • head and neck cancer
  • intensity-modulated radiation therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer. / Kao, Johnny; Genden, Eric M.; Gupta, Vishal; Policarpio, Edelweiss L.; Burri, Ryan J.; Rivera, Michael; Gurudutt, Vivek; Som, Peter M.; Teng, Marita; Packer, Stuart.

In: Cancer, Vol. 117, No. 2, 15.01.2011, p. 318-326.

Research output: Contribution to journalArticle

Kao, Johnny ; Genden, Eric M. ; Gupta, Vishal ; Policarpio, Edelweiss L. ; Burri, Ryan J. ; Rivera, Michael ; Gurudutt, Vivek ; Som, Peter M. ; Teng, Marita ; Packer, Stuart. / Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer. In: Cancer. 2011 ; Vol. 117, No. 2. pp. 318-326.
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abstract = "Background: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Method: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m 2), HU (500 mg twice daily), and cetuximab (250 mg/m2). Results: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83{\%}, 79{\%}, 69{\%}, and 86{\%}, respectively. Grade 3 toxicity consisted of mucositis in 33{\%} of patients, radiation dermatitis in 15{\%}of patients, anemia in 18{\%} of patients, leukopenia in 18{\%} of patients, neutropenia in 12{\%} of patients, and thrombocytopenia in 3{\%} of patients. Most patients (64{\%}) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≤4 adverse events. Conclusions: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.",
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AU - Genden, Eric M.

AU - Gupta, Vishal

AU - Policarpio, Edelweiss L.

AU - Burri, Ryan J.

AU - Rivera, Michael

AU - Gurudutt, Vivek

AU - Som, Peter M.

AU - Teng, Marita

AU - Packer, Stuart

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N2 - Background: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Method: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m 2), HU (500 mg twice daily), and cetuximab (250 mg/m2). Results: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≤4 adverse events. Conclusions: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.

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