title: Intensified concomitant chemoradiotherapy with and without filgrastim for poor-prognosis head and neck cancer.
abstract: OBJECTIVE
  We previously demonstrated high locoregional control rates in patients with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea (HU), and concomitant radiotherapy (FHX). In two trials reported here, we added cisplatin with and without granulocyte colony-stimulating factor (G-CSF) to 5-FU, HU, and concomitant radiotherapy.
  
  
  METHODS
  Eligible patients had failed to respond to prior local therapy (group 1); previously untreated patients with unresectable and/or metastatic disease and a projected 2-year survival rate less than 10% were also eligible (group 2). Chemoradiotherapy consisted of 1.8 to 2.0 Gy on days 1 to 5 with simultaneous infusional 5-FU at 800 mg/m2/d and HU administered every 12 hours for 11 doses at escalating doses. Cisplatin was administered at 100 mg/m2 during every other cycle. Cycles were repeated every 14 days until completion of radiotherapy. In study 2, G-CSF was added on days 6 to 13 at 5 micrograms/kg/d.
  
  
  RESULTS
  Acute and cumulative myelosuppression limited the feasibility of adding cisplatin to FHX without G-CSF. G-CSF allowed for escalation of HU to 1 g orally every 12 hours without dose-limiting acute toxicity during cycles 1 and 2. Dose-limiting cumulative toxicity consisted of severe or life-threatening myelosuppression and mucositis. To decrease total treatment duration and, thus, cumulative toxicity, a hyperfractionated radiation therapy schedule was investigated using the established chemotherapy doses with 1.5 Gy twice daily on days 1 to 5 (75 Gy over five treatment cycles). No increase in acute toxicities was seen; cumulative toxicities remained frequently severe or life-threatening. Thirty-eight of 45 assessable patients responded. The median survival duration was 12 months for both groups. Median time to treatment failure was 8 months for group 1 and has not been reached for group 2. At 1 year, local control rates were 74% and 91% for groups 1 and 2, respectively.
  
  
  CONCLUSIONS
  The addition of cisplatin to 5-FU, HU, and concomitant radiotherapy is feasible using G-CSF. The high locoregional control rate and failure-free interval justify further investigation of this regimen in previously untreated patients.
authors.affiliation: Department of Medicine, University of Chicago, IL.
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: J M
authors.initials: JM
authors.lastname: McEvilly
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim; D002945:Cisplatin; D005472:Fluorouracil; D006918:Hydroxyurea