title: A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  The authors conducted a Phase I/II study in patients with a poor prognosis who had locally advanced squamous cell carcinoma of the head and neck (SCCHN) and who were treated initially with induction chemotherapy. Patients were treated with weekly docetaxel and concurrent daily fractionated radiation therapy to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of the regimen.
  
  
  METHODS
  Twenty-two patients were enrolled, and 21 patients were treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN without distant metastases and were treated first with 2-3 cycles of induction chemotherapy, which consisted of cisplatin plus 5-fluorouracil with or without leucovorin. Patients with a poor prognosis were identified as those who achieved a partial response to induction treatment, achieved a complete response with a positive biopsy, or were at high risk for developing recurrent disease. Patients were treated subsequently with concurrent, escalating doses of docetaxel (given weekly x 6) and once daily 200-centigray radiation fractions.
  
  
  RESULTS
  Three patients were treated with a weekly docetaxel dose of 20 mg/m(2) without dose-limiting toxicity (DLT). Both patients who were treated at the next dose level of 30 mg/m(2) experienced DLT. A dose of 25 mg/m(2) was studied without DLT in the 16 patients who were treated, establishing this as the MTD. Sixty-seven percent of the patients are alive without disease at a median follow-up of 35 months (range, 12-59 months) after the initiation of chemoradiotherapy.
  
  
  CONCLUSIONS
  The MTD of weekly docetaxel with concurrent daily radiation therapy in the postinduction setting was 25 mg/m(2). Disease free survival data from this study were good and indicated that this regimen was effective in the treatment of patients with SCCHN who had a poor prognosis.
authors.affiliation: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. rtishler@caregroup.harvard.edu
authors.forename: Roy B
authors.initials: RB
authors.lastname: Tishler
authors.forename: Charles M
authors.initials: CM
authors.lastname: Norris
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Lamb
authors.forename: Daniel
authors.initials: D
authors.lastname: Karp
authors.forename: Paul M
authors.initials: PM
authors.lastname: Busse
authors.forename: Asa
authors.initials: A
authors.lastname: Nixon
authors.forename: Robert
authors.initials: R
authors.lastname: Frankenthaler
authors.forename: Bernadette
authors.initials: B
authors.lastname: Lake-Willcutt
authors.forename: Rosemary
authors.initials: R
authors.lastname: Costello
authors.forename: Maryann
authors.initials: M
authors.lastname: Case
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil