Randomized Trial of ARCON in Larynx Cancer

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

Sex

All

Minimum age

19 Years

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).

• DERIVEDJanssens GO, Langendijk JA, Terhaard CH, Doornaert PA, van den Ende P, de Jong MA, Takes RP, Span PN, Kaanders JH. Quality-of-life after radiotherapy for advanced laryngeal cancer: Results of a phase III trial of the Dutch Head and Neck Society. Radiother Oncol. 2016 May;119(2):213-20. doi: 10.1016/j.radonc.2016.02.023. Epub 2016 May 8. PMID 27165613
• DERIVEDJanssens GO, Rademakers SE, Terhaard CH, Doornaert PA, Bijl HP, van den Ende P, Chin A, Takes RP, de Bree R, Hoogsteen IJ, Bussink J, Span PN, Kaanders JH. Improved recurrence-free survival with ARCON for anemic patients with laryngeal cancer. Clin Cancer Res. 2014 Mar 1;20(5):1345-54. doi: 10.1158/1078-0432.CCR-13-1730. Epub 2014 Jan 22. PMID 24452791