title: Taxane-based chemoirradiation for organ preservation with locally advanced head and neck cancer: results of a phase II multi-institutional trial.
abstract: BACKGROUND
  The optimal drug schedule and sequencing of chemotherapy and radiation for organ preservation in head and neck cancer has yet to be determined. We undertook a phase II trial of a taxane-based induction chemotherapy (ICT) followed by a taxane-based concurrent chemoradiation (CCR) regimen in patients with resectable stage III or IV disease to determine the feasibility, toxicity, and overall efficacy.
  
  
  METHODS
  Forty-four patients with laryngeal or tongue base carcinomas were enrolled. All patients received 3 cycles of chemotherapy with paclitaxel 175 mg/m(2) and carboplatin AUC (area under the curve) 6-7.5 over 30 minutes on days 1, 22, and 43. Responding patients went on to receive radiation (70 Gy/7 weeks) with cisplatin 75 mg/m(2) IV on days 1, 22, and 43 and weekly paclitaxel 30 mg/m(2) IV (n = 22). Because of hematologic toxicity, the concurrent regimen was changed to weekly carboplatin AUC 1 plus weekly paclitaxel 30 mg/m(2) (n = 22).
  
  
  RESULTS
  Twenty-three patients with stage III and 21 patients with stage IV disease were enrolled. Median follow-up was 3.7 years. Acute toxicity of concurrent cisplatin and paclitaxel was excessive, with significant hematologic toxicity and 2 toxic deaths. Acute toxicities of concurrent carboplatin and paclitaxel were tolerable. No patients required permanent percutaneous gastrostomy tubes. The organ preservation rate was 83% (toxic deaths considered failures). Of 42 evaluable patients, 20 patients had complete responses (48%), 17 partial responses (41%), 3 minor responses (11%), 1 stable disease (2%), and 1 progressive disease (2%). Two-year local control, relapse-free survival, and overall survival were 82%, 77%, and 71%, respectively.
  
  
  CONCLUSIONS
  There were no significant differences in relapse-free survival or organ preservation rates between concurrent regimens. Platinum and paclitaxel-based CCR is feasible after ICT and provides a high rate of organ preservation. Substitution of concurrent cisplatin to weekly carboplatin with paclitaxel and radiation has an improved toxicity profile. The ease of administration and low toxicity make this a regimen that is practical for use in the community setting.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. anthony.cmelak@vanderbilt.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cmelak
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Murphy
authors.forename: Brian
authors.initials: B
authors.lastname: Burkey
authors.forename: Stacy
authors.initials: S
authors.lastname: Douglas
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: James
authors.initials: J
authors.lastname: Netterville
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel