title: Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Radiation Oncology, Duke University, Durham, NC, USA. brizel@radonc.duke.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Brizel
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Murphy
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: Kishan J
authors.initials: KJ
authors.lastname: Pandya
authors.forename: Stefan
authors.initials: S
authors.lastname: Glück
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Brizel
authors.forename: Ruby F
authors.initials: RF
authors.lastname: Meredith
authors.forename: Dietmar
authors.initials: D
authors.lastname: Berger
authors.forename: Mon-Gy
authors.initials: MG
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Mendenhall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use*; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D051523:Fibroblast Growth Factor 7; D002945:Cisplatin; D005472:Fluorouracil