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

• Published in: Cancer 2011-01, Vol.117 (2), p.318-326
• Main Authors: Kao, Johnny, Genden, Eric M., Gupta, Vishal, Policarpio, Edelweiss L., Burri, Ryan J., Rivera, Michael, Gurudutt, Vivek, Som, Peter M., Teng, Marita, Packer, Stuart H.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adolescent; Adult; Aged; Anemia; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - radiotherapy; Cetuximab; chemoradiation; Chemotherapy; Clinical trials; Combined Modality Therapy; Dermatitis; epidermal growth factor receptor; Feeding; Female; Fluorouracil - administration & dosage; Head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - radiotherapy; Humans; Hydroxyurea; Hydroxyurea - administration & dosage; intensity‐modulated radiation therapy; Leukopenia; Male; Medical sciences; Middle Aged; Mucositis; Neutropenia; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Quality of Life; Radiation; Radiotherapy, Intensity-Modulated; Risk groups; squamous cell carcinoma; Surgery; Survival; Thrombocytopenia; Toxicity; Tumors
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.25374

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/m2), 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. Cancer 2011. © 2010 American Cancer Society. In this phase 2 trial, the toxicity and efficacy of concurrent 5‐flurouracil, hydroxyurea, cetuximab, and hyperfractionated radiation therapy were studied in patients with advanced (stages III, IVA, and IVB) head and neck cancer. The results indicated that a concurrent schedule of 5‐flurouracil, hydroxyurea, and cetuximab plus simultaneous integrated‐boost, intensity‐modulated radiation is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for locally advanced head and neck cancer.