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.

Condition	Treatment or Intervention	Phase
stage II nasopharyngeal cancer stage III nasopharyngeal cancer stage IV nasopharyngeal cancer oral complications of cancer and cancer therapy Drug Toxicity radiation toxicity	Drug: amifostine  Drug: carboplatin  Drug: cisplatin  Drug: paclitaxel  Procedure: chemoprotection  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radioprotection  Procedure: supportive care/therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  15 Years   -   70 Years,  Genders Eligible for Study:  Both

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

Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Centre Antoine Lacassagne, Nice,  06189,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy
      Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova),  16132,  Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples,  80131,  Italy
      Ospedale Santa Croce, Cuneo,  12100,  Italy
Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
      Hospital General de Jerez, Jerez,  11407,  Spain
Turkey
      Istanbul University-Institute of Oncology, Istanbul,  34390,  Turkey
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom

Study chairs or principal investigators

Lisa Licitra, MD,  Study Chair,  Istituto Nazionale per lo Studio e la Cura dei Tumori   

Study ID Numbers:  CDR0000068947; EORTC-24981
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025298
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08