• Overall survival [ Time Frame: Indefinitely ] [ Designated as safety issue: No ]
  

• Distant failure-free survival (DFFS) [ Time Frame: Indefinitely ] [ Designated as safety issue: No ]
  
• failure pattern [ Time Frame: Indefinitely ] [ Designated as safety issue: No ]
  
• progression free survival [ Time Frame: Indefinitely ] [ Designated as safety issue: No ]
  
• quality of life (QOL) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  

TRIAL DESIGN:

Phase III trial of induction therapy with docetaxel followed by chemoradiotherapy versus chemoradiotherapy alone in patients with nodal stage N2 or N3 head and neck cancer

OBJECTIVES:

Primary

• To determine the effect on overall survival when induction chemotherapy is administered prior to chemoradiotherapy in patients with N2 or N3 disease.

Secondary

• To determine the effect of induction chemotherapy when administered prior to chemoradiotherapy on distant failure-free survival, failure pattern, progression free survival and quality of life.

TREATMENT PLAN:

• After eligibility is confirmed, patients will be randomized to one of two treatment arms:

Arm A - Induction + chemoradiotherapy

Arm B - Chemoradiotherapy alone

• Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (day 1), cisplatin (day 1), and 5-fluorouracil (days 1-5). Total duration of 6 weeks.
• Chemoradiotherapy: Five 14-day cycles of docetaxel (day 1), 5-fluorouracil (day 0-4), and hydroxyurea (days 0-4) with twice daily radiation (days 1-5). Total duration of 10 weeks.
• All patients will undergo surgical evaluation after chemoradiation for possible neck dissection.
• Upon completion of treatment, patients will be monitored every three months during the first year, every six months during the second and third years, and annually thereafter, up to five years.
• Patients will be followed for Quality of Life (QOL) during the course of treatment, as well as annually thereafter, up to five years.

PROJECTED ACCRUAL:

• An expected sample size of 400 patients will be enrolled for this study (200 per treatment arm).

Inclusion Criteria:

• Age 18 years or older
• Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck (excluding lip), or lymphoepithelioma
• No prior chemotherapy or radiotherapy
• Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor
• Karnofsky performance status of >= 70%
• Intact organ and bone marrow function
• Obtained informed consent

Exclusion Criteria:

• Demonstration of metastatic disease (i.e. M1 disease).
• Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea
• Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years.
• Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment.
• Incomplete healing from previous surgery
• Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician.
• Uncontrolled active infection unless curable with treatment of their cancer.