Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma.

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; DeltaN23-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/m(2) for 4 days and continuous-infusion fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 of irradiation. Patients were randomly assigned 2:1 to palifermin 60 microg/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 >or= 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 microg/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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 15 Pg. 2489-96 (May 20 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18487568 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Fibroblast Growth Factor 7
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy, secondary, therapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Fibroblast Growth Factor 7 (therapeutic use)
• Fluorouracil (administration & dosage)
• Head and Neck Neoplasms (drug therapy, pathology, radiotherapy, therapy)
• Humans
• Male
• Middle Aged
• Mucositis (etiology)
• Neoplasm Staging
• Prognosis
• Survival Rate