Randomized Trial of ARCON in Larynx Cancer

A Multicentre, Randomised, Phase III Clinical Trial Comparing Accelerated Radiotherapy With Accelerated Radiotherapy Plus Carbogen and Nicotinamide (ARCON) in Clinical Stage T2-4 Laryngeal Carcinoma.

TITLE:

A multicentre, randomised, phase III clinical trial comparing accelerated radiotherapy with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in clinical stage T2-4 laryngeal carcinoma.

PRIMARY OBJECTIVE:

Does the addition of carbogen and nicotinamide to a schedule of accelerated radiotherapy in patients with clinical stage T2-4 laryngeal carcinoma improve local primary tumour control? Definitive analysis will be performed on local control rates at two years after completion of radiotherapy.

SECONDARY OBJECTIVES:

Does the addition of carbogen and nicotinamide

• increase the larynx preservation rate?
• increase the regional control rate?
• increase the toxicity of accelerated radiotherapy?
• improve the overall quality of life?
• improve the disease-free survival?
• improve the overall survival?

STUDY DESIGN:

An open-label, randomised clinical trial assigning patients in a 1:1 ratio to one of the following treatment arms:

• accelerated radiotherapy
• accelerated radiotherapy plus carbogen and nicotinamide

PATIENT CHARACTERISTICS AND NUMBER:

344 patients with clinical T2-4 laryngeal carcinoma

MEASUREMENTS:

• time to local failure
• time to regional failure
• survival with functional larynx
• overall and disease-free survival
• frequency and severity of complications related to radiotherapy and carbogen and nicotinamide
• quality of life assessment

Inclusion Criteria:

• Pathological confirmed squamous cell carcinoma of the larynx.
• TNM-classification (UICC 1997, appendix I):
• T3-4 glottic or supraglottic carcinoma
• T2 glottic carcinoma with impaired cord mobility or subglottic extension
• T2 supraglottic carcinoma with invasion of mucosa of base of tongue or vallecula or invasion of the medial wall of the piriform sinus.
• any N-stage, M0.
• WHO performance status 0 or 1 (appendix II).
• Age > 18 years.
• Written informed consent.
• Quality of life questionnaire completed.

Exclusion Criteria:

• Prior or concurrent treatment for this tumour.
• Severe stridor and adequate debulking of airway not possible.
• Impaired renal function: serum creatinine above upper normal limit.
• Use of nefrotoxic medication (including ACE-inhibitors) that cannot be discontinued for the duration of the radiation treatment.
• Impaired hepatic function: ASAT and ALAT more than 1.5 times the upper normal limit.
• Use of anti-convulsants that cannot be discontinued for the duration of the radiation treatment.
• History of malignancy during the previous 5 years except basal cell carcinoma of skin, carcinoma in situ of the cervix, or superficial bladder neoplasm (pTa).