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

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Abstract

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; ΔN23-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.

Original languageEnglish
Pages (from-to)2489-2496
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number15
DOIs
StatePublished - Sep 15 2008
Externally publishedYes

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Fibroblast Growth Factor 7
Cohort Studies
Mucositis
Radiotherapy
Placebos
Chemoradiotherapy
Carcinoma, squamous cell of head and neck
Drug Therapy
Xerostomia
Survival
Head and Neck Neoplasms
Deglutition Disorders
Fluorouracil
Cisplatin
Neoplasms
Therapeutics
Epithelium

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Brizel, D. M., Murphy, B. A., Rosenthal, D. I., Pandya, K. J., Glück, S., Brizel, H. E., ... Mendenhall, W. (2008). Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. Journal of Clinical Oncology, 26(15), 2489-2496. https://doi.org/10.1200/JCO.2007.13.7349

Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. / Brizel, David M.; Murphy, Barbara A.; Rosenthal, David I.; Pandya, Kishan J.; Glück, Stefan; Brizel, Herbert E.; Meredith, Ruby F.; Berger, Dietmar; Chen, Mon Gy; Mendenhall, William.

In: Journal of Clinical Oncology, Vol. 26, No. 15, 15.09.2008, p. 2489-2496.

Research output: Contribution to journalArticle

Brizel, DM, Murphy, BA, Rosenthal, DI, Pandya, KJ, Glück, S, Brizel, HE, Meredith, RF, Berger, D, Chen, MG & Mendenhall, W 2008, 'Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma', Journal of Clinical Oncology, vol. 26, no. 15, pp. 2489-2496. https://doi.org/10.1200/JCO.2007.13.7349
Brizel, David M. ; Murphy, Barbara A. ; Rosenthal, David I. ; Pandya, Kishan J. ; Glück, Stefan ; Brizel, Herbert E. ; Meredith, Ruby F. ; Berger, Dietmar ; Chen, Mon Gy ; Mendenhall, William. / Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 15. pp. 2489-2496.
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AU - Glück, Stefan

AU - Brizel, Herbert E.

AU - Meredith, Ruby F.

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N2 - 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; ΔN23-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.

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