RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have previously untreated advanced cancer of the mouth, pharynx, or larynx.

Condition	Treatment or Intervention	Phase
stage IV squamous cell carcinoma of the lip and oral cavity stage IV squamous cell carcinoma of the nasopharynx stage III squamous cell carcinoma of the hypopharynx stage IV lymphoepithelioma of the oropharynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the lip and oral cavity stage IV squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the hypopharynx stage IV lymphoepithelioma of the nasopharynx	Procedure: chemotherapy  Procedure: surgery  Procedure: radiation therapy  Procedure: conventional surgery  Drug: carboplatin  Drug: fluorouracil  Drug: hydroxyurea  Drug: paclitaxel	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the activity of induction chemotherapy with carboplatin and paclitaxel followed by concurrent fluorouracil, hydroxyurea, paclitaxel, and hyperfractionated radiotherapy in terms of response rate, pattern of failure, time to progression, and overall survival in patients with previously untreated advanced oral, pharyngeal, or laryngeal cancer. II. Assess this treatment regimen in terms of the pattern and degree of clinical acute, cumulative, and chronic toxic effects in this patient population. III. Assess the rate of organ preservation in resectable patients treated with this regimen. IV. Evaluate the quality of life, organ function, and incidence of second primary tumors in patients treated with this regimen. V. Assess the rate of complications with subcutaneously implanted IV infusion catheters in patients treated with this regimen.

PROTOCOL OUTLINE: Patients receive induction chemotherapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes weekly for 3 weeks. Treatment repeats every 4 weeks for 2 courses. At 1-2 weeks after completion of induction chemotherapy, patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, radiotherapy twice daily on days 1-5, and paclitaxel IV over 1 hour on day 2. Treatment repeats every 2 weeks for 5 courses. Patients with residual nodal disease or initially staged nodal disease in the absence of macroscopic residual disease undergo neck dissection after completion of chemoradiotherapy. Patients with residual disease at the primary site undergo complete excision of disease. Patients with disease progression or disease recurrence are considered for conventional surgical management. Quality of life is assessed every 3 months for 6 months, every 6 months for 1.5 years, and then annually thereafter. Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 12-18 months.

Ages Eligible for Study:  15 Years   -   80 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically or cytologically confirmed squamous cell or poorly differentiated carcinomas, or lymphoepithelioma of the head and neck

• Stage III carcinoma of the base of the tongue or hypopharynx
• Stage IV carcinoma of the oral cavity, pharynx (including nasopharynx, oropharynx, and hypopharynx), or larynx

No distant metastasis

Measurable disease desirable

• Clinically disease free after prior surgery allowed

--Prior/Concurrent Therapy--

Biologic therapy: Not specified

Chemotherapy: No prior chemotherapy

Endocrine therapy: Not specified

Radiotherapy: No prior radiotherapy

Surgery:

• See Disease Characteristics
• Incisional or excisional biopsy and organ sparing procedures (e.g., debulking of airway compromising tumors or neck dissection) in patients with an existing primary tumor allowed
• No more than 3 months since prior nonbiopsy procedure

--Patient Characteristics--

Age: 15 to 80

Performance status: Karnofsky 60-100%

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal: Creatinine no greater than 2.0 mg/dL

Cardiovascular: No clinically significant cardiomyopathy or congestive heart failure

Pulmonary: No clinically significant pulmonary dysfunction

Other:

• No severe baseline neurologic deficits
• No uncontrolled active infection other than that not curable without treatment of cancer
• No sensitivity to Cremophor EL
• Not pregnant or nursing

Illinois
      Monroe Medical Associates, Chicago,  Illinois,  60603,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States

Study chairs or principal investigators

Athanassios Argiris,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000067310; NU-C98N1; NCI-G99-1587; UCCRC-9502
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004094
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08