SWOG-9451, Combination Chemo & RT For Patients With Stage III/Stage IV Cancer of the Hypopharynx or Tongue

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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.

Official Title
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Induction Chemotherapy Followed By Chemoradiation For Organ Preservation In Patients With Advanced Resectable Cancer Of The Hypopharynx And Base Of Tongue, Phase II

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Induction chemotherapy
* Drug: cisplatin
* Drug: fluorouracil
* Radiation: low-LET cobalt-60 gamma ray therapy


Participation Criteria
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Eligibility Criteria
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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 11/15/1998 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 PRIOR CONCURRENT THERAPY: No prior therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>induction chemotherapy followed by chemoradiation | Drug: Induction chemotherapy<br>* Cisplatin and 5-Fluorouracil<br>* Other names: 5-FU;Drug: cisplatin<br>* Cisplatin 100 mg/m2 IV infusion over 90 minutes Day 1 every 21 days for 2 cycles.<br>* Other names: platinol;Drug: fluorouracil<br>* 5-Fluorouracil 1,000 mg/m2/day continuous IV infusion over 24 hours Days 1 through 5 every 21 days for 2 cycles.<br>* Other names: 5-FU;Radiation: low-LET cobalt-60 gamma ray therapy<br>* 180 cGy per day, Days 1-5, every week for eight weeks<br>* Other names: RT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | Complete disappearance of all measurable and evaluable disease. No new lesions, No disease related symptoms. No evidence of non-evaluable disease, including normalization of markers and other abnormal lab values. Specifically, the rate of organ preservation (no surgery required at the primary tumor site). | 23 to 27 weeks after beginning treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx