Chemotherapy and Radiation Therapy in Treating Patients With Stage III or Stage IV Larynx or Oropharynx Cancer

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 chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by radiation therapy and chemotherapy in treating patients who have stage III or stage IV cancer of the larynx or stage III or stage IV cancer of the oropharynx.

Detailed Description
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OBJECTIVES: Determine the organ preservation rate in patients with stage III or IV squamous cell carcinoma of the larynx or oropharynx treated with paclitaxel and carboplatin followed by paclitaxel with concurrent radiotherapy. Determine the feasibility and toxicity of this regimen in these patients. Determine the utility of pre- and post-treatment organ function instruments on swallowing ability and voice quality in patients treated with this regimen. Determine the disease-free survival and patterns of failure of patients treated with this regimen. Determine the objective tumor response rate (complete and partial response) in these patients following treatment with 2 courses of induction therapy with paclitaxel and carboplatin. Determine changes in quality of life of patients treated with this regimen. Determine whether the presence of human papilloma virus infection and p-glycoprotein correlates with outcome in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to disease site (larynx vs oropharynx). Patients receive induction therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on days 1 and 22. Within 28 days after completion of induction therapy, patients with responding or stable disease receive paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and radiotherapy once daily, 5 times weekly, for 7 weeks beginning on day 1. Within 6-8 weeks after completion of therapy, patients who initially had bulky neck disease (N3) or who have residual palpable lymphadenopathy undergo surgical neck dissection. Patients with N1-N2 disease with complete response may also undergo neck dissection. Patients with initial complete response who recur at the primary site undergo surgical salvage. Quality of life is assessed at baseline, after induction therapy, and at 3, 12, and 24 months after completion of all therapy. Patients are followed at 6 weeks, 3 months, every 6-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 5 years thereafter. PROJECTED ACCRUAL: A total of 110 patients (55 per stratum) will be accrued for this study.

Official Title
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A Phase II Trial OF Chemoradiation For Organ Preservation In Resectable Stage III or IV Squamous Cell Carcinomas Of The Larynx Or Oropharynx

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage III or IV (T2-T4) squamous cell carcinoma of the larynx or oropharynx No recurrent disease No evidence of distant metastasis Resectable disease, defined as follows: High probability of attaining clear surgical margins (for disease of the base of tongue, tonsil, soft palate, or pharyngeal wall) No extension to root of tongue (for disease of the base of tongue) No extension into pterygoid by radiograph (for disease of the tonsil, soft palate, or pharyngeal wall) No primary tumor or nodal metastases fixed to the carotid artery or cervical spine (for disease of the base of tongue, tonsil, soft palate, or pharyngeal wall) No trismus (for disease of the tonsil, soft palate, or pharyngeal wall) No involvement of the trachea greater than 1 cm or any involvement of the esophagus (for disease of the subglottis) For disease of the supraglottis, glottis, or subglottis: No base of the tongue invasion greater than 2 cm No tumor extension through cartilage to involve strap muscles of the neck No tumor fixation to prevertebral fascia No involvement of the carotid artery No fixed nodal disease with involvement of the deep neck Extension into pyriform sinus or lateral pharyngeal wall allowed if no extension into posterior pharynx Measurable disease - Lesions accurately measured in at least one dimension as > 20 mm (2.0 cm) with conventional techniques or as > 10 mm (1.0 cm) with spiral CT scan Cytologic or histologic evidence of neoplasm is needed for measurable disease restricted to a solitary lesion No other concurrent head and neck neoplasms PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Not specified Renal Creatinine less than 3.0 mg/dL Calcium normal Cardiovascular No significant cardiac disease No uncontrolled hypertension No unstable angina No congestive heart failure No myocardial infarction within the past year No serious cardiac arrhythmias requiring medication Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study completion No significant detectable infection No history of allergy to drugs containing Cremophor EL No history of allergy to mammalian cell-derived products (epoetin alfa) or human albumin No other malignancy within the past 3 years except basal or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy No concurrent amifostine Endocrine therapy Not specified Radiotherapy No prior radiotherapy above the clavicles Surgery No prior surgery to the primary tumor except biopsy or debulking Other No concurrent experimental mucosal protectants

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Procedure: conventional surgery|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ preservation rate |  |  | 
| Feasibility and toxicity |  |  | 
| Utility of pre- and post-treatment organ function instruments |  |  | 
| Disease-free survival and patterns of failure |  |  | 
| Objective tumor response rate (complete and partial response) |  |  | 
| Changes in quality of life |  |  | 
| Correlation of the presence of human papilloma virus infection and p-glycoprotein with outcome |  |  | 

 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 larynx, stage IV squamous cell carcinoma of the larynx