title: Phase I and initial phase II results from a trial investigating weekly docetaxel and carboplatin given neoadjuvantly and then concurrently with concomitant boost radiotherapy for locally advanced squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  The current Phase I/II study assessed induction docetaxel/carboplatin given weekly for 4 weeks, followed by weekly docetaxel/carboplatin and concomitant boost radiotherapy (CB-XRT) for locally advanced head and neck squamous cell carcinoma.
  
  
  METHODS
  Twenty patients with Stage III or IV (M0) disease of the oropharynx, supraglottic larynx, or hypopharynx were enrolled. Patients initially received docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly x 4. Patients with stable (SD) or responding disease subsequently received dose-escalated docetaxel (10-20 mg/m2 in sequential patient cohorts) and carboplatin AUC 1 weekly x 5 with CB-XRT (1.8 gray [Gy] every day x 15 days, followed by 1.8/1.5 Gy twice per day x 13 days).
  
  
  RESULTS
  All patients were evaluable, and 15 patients (5 patients with Stage III disease, 10 patients with Stage IV disease) completed all planned therapy. The target docetaxel dose level of 20 mg/m(2) weekly with radiotherapy was achieved with no dose-limiting toxicities. The most frequent maximum toxicities during chemoradiotherapy were Grade 3 mucositis, dysphagia, and/or pain. Primary site responses after induction included 4 patients with partial responses, 11 patients with SD, and 5 patients with disease progression. Fifteen patients (75%) continued to receive chemoradiotherapy, with 14 patients attaining a complete response (CR). Overall, a clinicopathologic neck CR after chemoradiotherapy was achieved in 9 of 10 patients. One patient had persistent primary disease and underwent salvage surgery, whereas another died of unrelated causes before neck assessment. Thirteen patients remain free of any disease event, with a median follow-up of 15 months (range, 3-29 months).
  
  
  CONCLUSIONS
  This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. Initial induction response results suggested that further investigation of this regimen with more aggressive induction therapy is warranted.
authors.affiliation: Radiation Oncology Service, Seattle VA Puget Sound Health Care System, Seattle, Washington, USA. docdls@mdanderson.org
authors.forename: David L
authors.initials: DL
authors.lastname: Schwartz
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Montgomery
authors.forename: Bevan
authors.initials: B
authors.lastname: Yueh
authors.forename: Michael
authors.initials: M
authors.lastname: Donahue
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Anzai
authors.forename: Raylene
authors.initials: R
authors.lastname: Canby
authors.forename: Raelene
authors.initials: R
authors.lastname: Buelna
authors.forename: Leslie
authors.initials: L
authors.lastname: Anderson
authors.forename: Charles
authors.initials: C
authors.lastname: Boyd
authors.forename: Janice
authors.initials: J
authors.lastname: Hutson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Keegan
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin