Chemotherapy Plus Radiation Therapy With or Without Amifostine in Treating Patients With Locally Advanced Cancer of the Nasopharynx

Study Overview
=================
Brief Summary
-----------------
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. Giving chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy and radiation therapy. PURPOSE: Randomized phase II trial to compare the effectiveness of paclitaxel and carboplatin followed by cisplatin plus radiation therapy with or without amifostine in treating patients who have locally advanced cancer of the nasopharynx.

Detailed Description
-----------------
OBJECTIVES: Compare the overall incidence of grade 3 or 4 mucositis in patients with locally advanced undifferentiated nasopharyngeal cancer treated with paclitaxel and carboplatin followed by cisplatin and radiotherapy with or without amifostine. Compare the feasibility and activity of these regimens in these patients. Determine the toxicity of paclitaxel and carboplatin in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to WHO performance status (0 vs 1 vs 2), response to induction chemotherapy (complete vs partial vs stable disease vs not evaluable), and participating center. Patients receive induction chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete or partial response after 2 courses of induction chemotherapy receive 2 additional courses before randomization. Patients with stable disease after 2 courses of induction chemotherapy or who cannot be evaluated after 1 course proceed directly to randomization. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin IV on days 1, 22, and 43. Patients also undergo radiotherapy daily 5 days a week for 6.5 weeks. Arm II:Patients receive amifostine subcutaneously daily. Patients receive chemotherapy and radiotherapy as in arm I. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 41-93 patients will be accrued for this study.

Official Title
-----------------
A Feasibility Study Of Primary Chemotherapy Followed By Concomitant Chemoradiation With And Without Amifostine In Patients With Locally Advanced Undifferentiated Nasopharyngeal Cancer (UNPC)

Conditions
-----------------
Drug/Agent Toxicity by Tissue/Organ, Head and Neck Cancer, Oral Complications, Radiation Toxicity

Intervention / Treatment
-----------------
* Drug: amifostine trihydrate
* Drug: carboplatin
* Drug: cisplatin
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed undifferentiated nasopharyngeal cancer (UNPC) Locoregionally advanced disease T2b, N1 (greater than 3 cm) or N2 T3, N1 (greater than 3 cm) or N2 T4, N1 (greater than 3 cm) or N2 Any T, N3 No squamous cell histology At least 1 unidimensionally measurable target lesion At least 20 mm by conventional techniques OR At least 10 mm by spiral CT scan No evidence of distant metastases No signs or symptoms of CNS metastases PATIENT CHARACTERISTICS: Age: 15 to 70 Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 2,000/mm^3 Platelet count at least 150,000/mm^3 Hemoglobin at least 12 g/dL Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST/ALT no greater than 2.5 times ULN Renal: Creatinine clearance at least 70 mL/min Calcium normal Cardiovascular: No hypotension or hypertension requiring therapy No prior myocardial infraction No pre-existing uncontrolled cardiac disease No signs of cardiac failure No rhythm disturbances requiring medication Other: No sensory neuropathy grade 2 or greater unless due to cranial nerve No uncontrolled infections No sensitivity to aminothiol compounds No other malignancy within the past 5 years except adequately controlled carcinoma in situ of the cervix or basal cell or squamous cell skin cancer No psychological, familial, sociological, or geographical condition that would preclude study Fertile patients must use effective contraception during and for 3 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No prior chemotherapy for UNPC Endocrine therapy: No concurrent hormonal therapy except corticosteroids for antiemetic prophylaxis Radiotherapy: No prior radiotherapy for UNPC Surgery: No prior surgery for UNPC except cervical lymphadenectomy Other: At least 1 month since prior investigational agent No other concurrent anticancer drugs

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: amifostine trihydrate|nan|
|Drug: carboplatin|nan|
|Drug: cisplatin|nan|
|Drug: paclitaxel|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
radiation toxicity, oral complications, stage II nasopharyngeal cancer, stage III nasopharyngeal cancer, stage IV nasopharyngeal cancer, drug/agent toxicity by tissue/organ