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 drug and combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for advanced head and neck cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy plus radiation therapy in treating patients who have advanced head and neck cancer.

Condition	Treatment or Intervention	Phase
stage IV squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the hypopharynx	Procedure: chemotherapy  Procedure: radiation therapy  Drug: cisplatin  Drug: docetaxel  Drug: fluorouracil	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the progression free survival of patients with locally advanced, inoperable squamous cell carcinoma of the head and neck treated with cisplatin plus fluorouracil with or without docetaxel as a neoadjuvant to radiotherapy. II. Compare the response rate, response duration, toxicity, local symptoms, and time to disease progression of these treatment regimens in this patient population. III. Evaluate the quality of life in these patients.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to primary tumor site (oral cavity vs oropharynx vs hypopharynx vs larynx) and institution. Patients are randomized to one of two treatment arms. Arm I: Patients receive docetaxel IV over 1 hour, immediately followed by cisplatin IV over 1 hour on day 1 and fluorouracil (5-FU) IV as a continuous infusion on days 1-5. Arm II: Patients receive cisplatin IV over 1 hour on day 1 followed by 5-FU IV as a continuous infusion on days 1-5. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive radiotherapy following chemotherapy within 3-6 weeks of last course. Radiotherapy is administered 5 days a week for up to 7 weeks. Quality of life is assessed before treatment, at courses 2 and 4, and at 6 and 9 months. Patients are followed every 3 months for the first 2 years and then every 6 months until death.

PROJECTED ACCRUAL: A total of 348 patients will be accrued for this study within 24 months.

Ages Eligible for Study:  18 Years   -   70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven locally advanced squamous cell carcinoma of the head and neck; Stage III or IV without distant metastases; Unresectable
• Primary tumor sites: Oral cavity; Oropharynx; Hypopharynx; Larynx
• Must have at least one measurable lesion

--Prior/Concurrent Therapy--

• Biologic therapy: No primary prophylactic colony stimulating factors during the first course of therapy
• Chemotherapy: No prior or concurrent chemotherapy
• Endocrine therapy: At least 3 weeks since prior corticosteroid; No chronic corticosteroid therapy (greater than 3 months)
• Radiotherapy: No prior radiotherapy
• Surgery: No prior surgery for this cancer
• Other: At least 30 days since prior treatment in a clinical trial; No concurrent use of drugs that interact with fluorouracil (e.g., cimetidine, allopurinol, folic acid or leucovorin calcium); No other concurrent investigational drugs or anticancer treatment

--Patient Characteristics--

• Age: 18 to 70
• Performance status: WHO 0-1
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 2,000/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: Bilirubin no greater than upper limit of normal (ULN); SGOT and SGPT no greater than 2.5 times ULN; Alkaline phosphatase no greater than 5 times ULN; No SGOT and SGPT greater than 1.5 times ULN AND alkaline phosphatase greater than 2.5 times ULN
• Renal: Creatinine no greater than 1.4 mg/dL OR Creatinine clearance at least 60 mL/min
• Cardiovascular: At least 6 months since prior myocardial infarction; No unstable, treated cardiac disease
• Pulmonary: At least one year since prior hospitalization for chronic obstructive pulmonary disease
• Neurologic: No neurologic or psychiatric disorders (e.g., dementia or seizures); No concurrent peripheral neuropathy greater than grade 1
• Other: No active uncontrolled infection; No active peptic ulcer; No alteration in hearing; At least 5 years since any other neoplastic disease except curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated by surgery; Not pregnant or nursing; Fertile patients must use effective contraception; No other psychological, familial, sociological, or geographical condition that would prevent compliance

Austria
      Allgemeines Krankenhaus der Stadt Wien, Vienna,  A-1090,  Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria
      Landeskrankenhaus/Universitatskliniken Graz, Graz,  A-8036,  Austria
Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Centre Hospitalier Regional de la Citadelle, LIEGE,  4000,  Belgium
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Oscar Lambret, Lille,  59020,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR Hotel Dieu, Nantes,  44093,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
Germany
      Caritasklinik St. Theresia, Saarbrucken,  D-66113,  Germany
      Martin Luther Universitaet, Halle,  DOH-0-6112,  Germany
      Mutterhaus der Borromaerinnen, Trier,  D-54219,  Germany
Greece
      Ahepa University Hospital, THESSALONIKI,  54636,  Greece
Hungary
      Borsod-Abauj-Zemplen County Hospital, Miskolc,  3501,  Hungary
      National Institute of Oncology, Budapest,  1125,  Hungary
      Szent Margit Hospital, Budapest,  3761,  Hungary
Italy
      Centro di Riferimento Oncologico - Aviano, Aviano,  33081,  Italy
      Istituti Fisioterapici Ospitalieri - Roma, Rome,  00161,  Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy
      Ospedale Santa Croce, Cuneo,  12100,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
Spain
      Hospital Clinico Universitario de Valencia, Valencia,  46010,  Spain
      Hospital General de Jerez, Jerez,  11407,  Spain
      Institut Catala d'Oncologia - Hospital Duran i Reynals, Barcelona,  08907,  Spain
      Universidad de Santiago - Hospital de Conxo, Santiago de Compostela,  Spain
Switzerland
      Kantonspital Aarau, AARAU,  5001,  Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland
Turkey
      Istanbul University-Institute of Oncology, Istanbul,  34390,  Turkey
United Kingdom, England
      Charing Cross Hospital, London,  England,  W6 8RF,  United Kingdom
      Middlesex Hospital- Meyerstein Institute, London,  England,  WIT 3AA,  United Kingdom
      Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom
Yugoslavia
      Institute of Oncology and Radiology of Serbia, Belgrade,  11000,  Yugoslavia

Study chairs or principal investigators

Jan Baptist Vermorken,  Study Chair,  EORTC Head and Neck Cancer Cooperative Group   

Study ID Numbers:  CDR0000067057; EORTC-24971; RP-56976-V-323
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003888
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08