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Phase II Study of Palifermin and Concurrent Chemoradiation in Head and Neck Squamous Cell Carcinoma

David M. Brizel, Barbara A. Murphy, David I. Rosenthal, Kishan J. Pandya, Stefan Glück, Herbert E. Brizel, Ruby F. Meredith, Dietmar Berger, Mon-Gy Chen, William Mendenhall

From the Departments of Radiation Oncology and Surgery, Duke University, Durham, NC; Department of Medical Oncology, Vanderbilt University, Nashville, TN; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA; Department of Medicine and Oncology, University of Rochester, Rochester, NY; Division of Hematology Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami; Department of Radiation Oncology, Memorial Hospital, Hollywood, FL; Department of Radiation Oncology, University of Florida, Gainesville, FL; Department of Radiation Oncology, University of Alabama, Birmingham, AL; and Clinical Development and Biostatistics, Amgen Inc, Thousand Oaks, CA

Corresponding author: David Brizel, MD, Duke University Medical Center, 05135 Morris Bld, Durham, NC 27710; e-mail: brizel{at}radonc.duke.edu

Purpose Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer. Palifermin (a recombinant human keratinocyte growth factor; N23-KGF) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers. This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma.

Patients and Methods In a phase II trial, standard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy, or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy, over 7 weeks. Chemotherapy included cisplatin 20 mg/m² for 4 days and continuous-infusion fluorouracil 1,000 mg/m²/d for 4 days on weeks 1 and 5 of irradiation. Patients were randomly assigned 2:1 to palifermin 60 µg/kg or placebo once weekly for 10 doses. A follow-up trial evaluated long-term survival.

Results Sixty-seven patients received palifermin and 32 received placebo. The median duration of grade 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups, respectively (P = .157). Palifermin appeared to reduce mucositis, dysphagia, and xerostomia during hyperfractionated radiotherapy (n = 40) but not standard radiation therapy (n = 59). Adverse events were similar between treatment groups. Palifermin did not alter tumor response or survival.

Conclusion Ten once-weekly doses of palifermin at 60 µg/kg were well tolerated. Most patients completed treatment, but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy. Future studies should evaluate higher palifermin doses with longer and more standardized assessment of acute mucositis.

Supported by Amgen Inc.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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