title: Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck: the Dana Farber Cancer Institute experience.
abstract: BACKGROUND
  The authors conducted a series of four Phase I-II trials of high-dose and intermediate-dose docetaxel, cisplatin, and 5-fluorouracil (TPF)-based induction chemotherapy for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). The chemotherapy regimens and response rates for each trial were published previously. In the current analysis, the authors report the data on long-term survival, patterns of failure, and morbidity among the patients who were treated at their institution.
  
  
  METHODS
  A total of 101 patients with previously untreated, locally advanced, curable SCCHN were entered onto the studies. Overall, 68 patients (67%) had N2-N3 disease, and 86 patients (85%) had Stage IV disease. Patients were treated with combinations of TPF with or without leucovorin. Cycles were repeated every 21-28 days for a total of 3 cycles followed by hyperfractionated radiotherapy.
  
  
  RESULTS
  After a median follow-up of 49 months, 65 patients (64%) remain alive with no evidence of disease (NED), and 3 patients remain alive with disease, for an overall survival rate of 67% (68 patients). Twenty-six patients had locoregional recurrences (LRR), and 5 patients had both LRR and distant metastasis (DM). Only five patients had DM as the sole site of failure. Four patients underwent salvage surgery at the primary site and remain alive with NED. Excluding 17 patients with nasopharyngeal carcinoma, of 84 patients, 55 patients remain alive with NED (65%). Notably, 43 of 84 patients (51%) had oropharyngeal primary tumors, and 30 of those patients remain alive with NED (70%). Significant morbidity was low, with two treatment-related deaths. All but two of the surviving patients are able to swallow and had their feeding tubes removed.
  
  
  CONCLUSIONS
  These data suggest that docetaxel adds incrementally to the efficacy of cisplatin and fluorouracil. Local-regional failures continue to be the major impediment to cure in these patients. Given the increase in local-regional dose intensity with chemoradiation, sequential treatment plans that integrate induction chemotherapy and chemoradiotherapy seem to be the logical next step.
authors.affiliation: Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. robert_haddad@dfci.harvard.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Haddad
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Roy
authors.initials: R
authors.lastname: Tishler
authors.forename: Paul
authors.initials: P
authors.lastname: Busse
authors.forename: Laura
authors.initials: L
authors.lastname: Goguen
authors.forename: Christopher
authors.initials: C
authors.lastname: Sullivan
authors.forename: Charles M
authors.initials: CM
authors.lastname: Norris
authors.forename: Bernadette
authors.initials: B
authors.lastname: Lake-Willcutt
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Case
authors.forename: Rosemary
authors.initials: R
authors.lastname: Costello
authors.forename: Marshall
authors.initials: M
authors.lastname: Posner
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077143:Docetaxel; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D043823:Taxoids; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil