Combination Chemotherapy Plus Radiation Therapy To Preserve the Larynx in Patients With Cancer of the Hypopharynx or Larynx

Head and Neck Cancer Clinical Trial

Official title:

PHASE II STUDY ON LARYNX PRESERVATION COMPARING INDUCTION CHEMOTHERAPY AND RADIOTHERAPY VERSUS ALTERNATING CHEMO-RADIOTHERAPY IN RESECTABLE HYPOPHARYNX AND LARYNX CANCERS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002839
• Other study ID #: EORTC-24954
• Status: Completed
• Phase: Phase 3
• Start date: July 1996

Study information

• Verified date: July 2018
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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: Randomized phase 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 564
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Laryngeal Diseases

Intervention

Drug:
• cisplatin

• fluorouracil

Procedure:
• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Centre Regional Francois Baclesse	Caen
France	Centre de Lutte Contre le Cancer, Georges-Francois Leclerc	Dijon
France	Centre Hospitalier Universitaire de Dijon	Dijon
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Centre Oscar Lambret	Lille
France	CRLCC Nantes - Atlantique	Nantes-Saint Herblain
France	Centre Antoine Lacassagne	Nice
France	Hopital Charles Nicolle	Rouen
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
Israel	Rambam Medical Center	Haifa
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Milano (Milan)
Italy	Ospedale Civile Monselice	Monselice, Padova
Italy	Azienda Ospedaliera "Santa Maria Degli Angeli"	Pordenone
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Israel,  Italy,  Netherlands,  Switzerland, 

References & Publications (2)

Lefebvre J, Horiot J, Rolland F, et al.: Phase III study on larynx preservation comparing induction chemotherapy and radiotherapy versus alternating chemoradiotherapy in resectable hypopharynx and larynx cancers. EORTC protocol 24954-22950. [Abstract] J C

Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Grou — View Citation