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 more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and radiation therapy in treating patients with stage III or stage IV cancer of the hypopharynx or tongue.

Condition	Treatment or Intervention	Phase
stage III squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the hypopharynx	Drug: cisplatin  Drug: fluorouracil	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the complete histologic response rate (which represents the rate of organ preservation) to induction with cisplatin/fluorouracil followed by radiotherapy plus cisplatin in patients with selected stage III/IV cancer of the hypopharynx or base of the tongue.

II. Evaluate the feasibility of accruing and treating patients with this regimen in a multi-institutional setting.

III. Determine the overall complete response rate in these patients.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to center and tumor site (hypopharynx vs base of tongue). Base of tongue stratum closed as of November 15, 1998.

Regimen A: Patients receive cisplatin IV over 90 minutes on days 1 and 22 and fluorouracil IV over 120 minutes on days 1-5 and 22-26. Patients with measurable neck nodes discontinue therapy if disease has progressed by day 22. All patients who achieve complete or partial response at day 43 proceed to regimen B. All others proceed to resection followed by radiotherapy (off study).

Regimen B (begins within 3-4 weeks of start of second induction course): Patients receive cisplatin IV over 90 minutes every 3 weeks for 3 courses. Concurrently, patients receive radiotherapy 5 days a week for 5.6 weeks.

Patients are reassessed at 8-12 weeks after radiotherapy. Patients who are disease free are observed. Other patients undergo surgical resection of nodes and/or primary tumor.

Patients are followed every 4-6 weeks for 1 year, every 2 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, then annually thereafter.

PROJECTED ACCRUAL: Up to 70 patients (35/tumor site) will be accrued for this study over 3.5 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed squamous cell carcinoma of the hypopharynx or base of the tongue that is newly diagnosed and considered resectable; For hypopharyngeal cancer, total laryngectomy would be required surgery
• Disease staged by clinical exam, endoscopy, and CT or MRI; Stage III that is T2-3 N0-1 M0; Stage IV that is T2-3 N2-3 M0
• Measurable or evaluable disease other than pleural effusion, ascites, or disease documented by indirect evidence
• Closed to patients with cancer of the base of tongue as of 11/15/98

--Prior/Concurrent Therapy--

• No prior therapy

--Patient Characteristics--

• Age: Adult
• Performance status: SWOG 0 or 1
• Hematopoietic: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 2 times normal; AST or ALT no greater than 3 times normal
• Renal: Creatinine no greater than 2 times normal; Creatinine clearance at least 60 mL/min; Magnesium normal (supplementation allowed)
• Other: Average hearing loss in both ears no greater than 40 dB in 50-2,000 Hz range; No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer; Carcinoma in situ of the cervix; Stage I/II cancer (other than head/neck) in complete remission; Not pregnant or nursing; Effective contraception required of fertile patients

Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      USC/Norris Comprehensive Cancer Center, Los Angeles,  California,  90033-0800,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Louisiana
      MBCCOP - LSU Medical Center, New Orleans,  Louisiana,  70112,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Missouri
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
New York
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States
Ohio
      Cleveland Clinic Cancer Center, Cleveland,  Ohio,  44195,  United States
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-1329,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States

Study chairs or principal investigators

Susan G. Urba,  Study Chair,  Southwest Oncology Group   

Study ID Numbers:  CDR0000064634; SWOG-9451
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002735
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08