A Randomized, Double Blind, Controlled, Multi-center, Phase III Study to Assess Efficacy of Low Level Diode Laser (100 MW, 658 Nm), in the Prevention and Treatment of Radiochemotherapy-induced Mucositis in Head and Neck Cancer.
This is a Phase III randomized, double-blind, multicenter study, with two groups of patients
receiving radiotherapy and concomitant chemotherapy.
The patients will be randomized as follows: Arm A = patients will receive a preventive and
curative treatment by low-energy laser, and arm B = a control group treated with standard
local treatments and a placebo laser (laser nonfunctional).
Randomization will be balanced in a ratio 1: 1 and stratified by the investigator site.
Assessments of mucositis, nutritional status, tolerance of the laser and pain will be
performed throughout the treatment, once a week, by an investigator unaware of the patients
treatment arm. The locoregional control will be evaluated every 3 months during the first
year, then every 6 months up to 5 years. In case of progression, treatments undertaken and
their results should be reported.
Radiotherapy: All patients will be treated with conformal radiotherapy with or without IMRT.
The dose should be adapted to the treatment indication (exclusive or postoperative) and the
histological findings in case of tumoral resection.
The radiotherapy will be prescribed in accordance with the recommendations of the ICRU 50
report. The dose delivered will always be 2 Gy per day 5 times a week. All beams will be
treated in each session. A radiological audit will be conducted for each beam treated by
photons in the first session and at least once a week.
Several chemotherapies concomitant to radiotherapy are possible:
- a combination of 5-FU and Cisplatin
- a combination of 5-FU and Carboplatin
- Cisplatin alone
- Cetuximab alone
Dental care: All patients (except edentulous) will be seen in odontostomatology consultation
prior to the treatment for dental care if necessary or potential production of fluorinated
gutters During the treatment, all patients will receive oral care
The dosimetric study will concern the cross section, the frontal and sagittal planes through
the axis of the lateral beams.
Arm A : laser low-level energy functional The material used will be a diode laser of 100
mW, with a wavelength of 658 nm. Application will be made after each radiotherapy session in
an adapted room (low light intensity, possibility of ENT examination) on all grades superior
or equal to 2 stomatitis injuries. The application is painless, athermal, odorless and
completely silent. The patient will wear glasses for retinal protection. The operator will
also wear glasses for his protection but allowing nevertheless the view of the beams and its
The tumor areas macroscopically invaded will be excluded from the areas application.
The energetic dose delivered will be 4 J/cm2. The duration of the treatment for one will be
determined by a corresponding abacus : [t(s) = energy (J/cm2) x surface (cm2) / puissance
(W)]. The overall duration will be a few minutes varying depending on the surface to be
treated The usual dental care will be prescribed when required.
Arm B : laser low-level energy nonfunctional The procedure is identical to the one used in
arm A but the laser will not be functional. The period of application will be around one
minute. All applications will be performed by one single operator by center. The results
will be assessed once a week by another physician (or nurse specifically trained) in each
center, unaware of whether the patients had laser sessions or not, in order to respect the
"blinding". The assessment will be detailed on a specifique sheet, specifying the degree of
mucositis (WHO), the level of pain, body weight , type of feeding , any analgesic treatment
taken by the patient, quality of life specific questionnaire, and the possible end of
treatment or therapeutic modifications (number of cycles of chemotherapy, dosage).
The laser should be started as soon as a grade 2 mucositis (WHO) is observed and will be
continued throughout the radio-chemotherapy until improvement of the mucositis (grade <2).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
To evaluate the efficacy of preventive and curative low energy laser induced mucositis in patients receiving concomitant chemotherapy and radiotherapy for squamous cell carcinoma of the head and neck with stage III-IV
Eric JADAUD, MD
Institut de Cancerologie de l'Ouest - Paul Papin
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)