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 and allow doctors to preserve the part of the body where the cancer started. It is not yet known which regimen of cisplatin and fluorouracil combined with radiation therapy is more effective in treating resectable cancer of the hypopharynx or larynx.

PURPOSE: Randomizedphase III trial to compare the effectiveness of two regimens of cisplatin and fluorouracil combined with radiation therapy in preserving the larynx in patients who have resectable cancer of the hypopharynx or larynx.

Condition	Treatment or Intervention	Phase
stage II squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the hypopharynx stage IV squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx	Drug: cisplatin  Drug: fluorouracil  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare relapse-free survival and larynx preservation in patients with resectable hypopharyngeal or laryngeal cancer treated with sequential vs alternating cisplatin and fluorouracil and radiotherapy.
• Compare the health-related quality of life in patients treated with these regimens.
• Compare the cost-effectiveness of these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by performance status, disease site, tumor stage, node stage, and center.

Patients are randomized to one of two treatment arms. Both groups may receive either conventional radiotherapy in single daily fractions, 5 days per week, for 7 weeks (option 1) or hyperfractionated radiotherapy in 2 daily fractions, 5 days per week, for 4-5 weeks (option 2), according to institutional policy.

• Arm I: Patients receive cisplatin and fluorouracil every 3 weeks. Patients with a complete or partial response on day 42 receive 2 additional courses of chemotherapy followed by 7 weeks of radiotherapy beginning on day 80. After radiotherapy, patients with a complete remission enter follow-up; those with a partial remission proceed to surgery. Patients with stable or progressive disease proceed immediately to surgery with or without postoperative radiotherapy.
• Arm II: Patients receive cisplatin and fluorouracil every 3 weeks for 4 courses. Patients treated on radiotherapy option 1 are evaluated 2 months after completion of radiotherapy; those with a complete remission enter follow-up while all others proceed to surgery. Patients treated on option 2 are evaluated on day 42; those with a partial or complete response complete chemoradiotherapy and are then evaluated and treated like option 1 patients. Patients with stable or progressive disease on day 42 proceed to surgery with or without a third course of chemotherapy on week 7. Patients are followed every 3 months for 3 years and at least every 6 months thereafter.

PROJECTED ACCRUAL: A total of 564 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven squamous cell carcinoma of the head and neck, including:
• Stage III/IV cancer of the glottic or supraglottic larynx
• Eligible T4 tumor defined as:
• Bulging the valleculae
• Bulging the hyothyroid membrane
• Minimal thyroid cartilage invasion or suspicion of invasion on imaging
• Stage II/III/IV cancer of the pyriform sinus or of the hypopharyngeal aspect of the aryepiglottic fold (with or without extension to postcricoid area)
• No massive destruction of the thyroid cartilage
• No continuity between primary tumor and a lymph node
• Operable on first attempt (as assessed by head and neck surgeon) by classical total laryngectomy with or without partial pharyngectomy
• No requirement for extended surgery (circumferential pharyngolaryngectomy)
• No tumor suitable for partial (functional) surgery or requiring extended surgery that necessitates any kind of flap for closure
• No N2c tumor unless no requirement for bilateral resection of internal jugular veins
• Measurable or evaluable disease by panendoscopy and CT scan or MRI
• Esophagoscopy required
• Bronchofiberscopy recommended
• No requirement for tracheotomy

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• WHO 0-2

Hematopoietic:

• WBC at least 4,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Other:

• No medical, psychological, or geographical condition that precludes study compliance
• No serious nonmalignant systemic disease
• No second malignancy except:
• Carcinoma in situ of the cervix
• Adequately treated nonmelanomatous skin cancer
• No poor nutritional status unlikely to be restored to fair status within 3 weeks
• No contraindication to CT scan or general anesthesia

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior anticancer biologic therapy

Chemotherapy

• No prior anticancer chemotherapy

Endocrine therapy

• No prior anticancer endocrine therapy

Radiotherapy

• No prior anticancer radiotherapy

Surgery

• See Disease Characteristics

Other

• No other prior anticancer therapy

Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre de Lutte Contre le Cancer, Georges-Francois Leclerc, Dijon,  21079,  France
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France
      Centre Hospitalier Universitaire de Dijon, Dijon,  21033,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
      Hopital Charles Nicolle, Rouen,  76031,  France
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
Italy
      Azienda Ospedaliera "Santa Maria Degli Angeli", Pordenone,  33170,  Italy
      Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan),  20133,  Italy
      Ospedale Civile Monselice, Monselice, Padova,  35043,  Italy
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Vrije Universiteit Medisch Centrum, Amsterdam,  1007 MB,  Netherlands
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland

Study chairs or principal investigators

Jean-Louis Lefebvre, MD,  Centre Oscar Lambret   
Jean-Claude Horiot, MD,  Centre de Lutte Contre le Cancer, Georges-Francois Leclerc   

Study ID Numbers:  CDR0000065056; EORTC-24954
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002839
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08