Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT

Inclusion Criteria:

• Squamous cell carcinoma of the larynx or hypopharynx, histologically proven, locallyadvanced:
• T2 not accessible to a supra-cricoid partial laryngectomy or not,
• T3 without massive infiltration by endolarynx transglottic injury,
• N0 to N2c
• No distant metastasis
• No associated cancer or earlier
• Patients Previously Untreated
• Age> 18 years and <75 years
• PS 0 or 1 according to WHO
• Tumor volume assessable by RECIST.
• Absence of distant metastasis, confirmed by chest TDM, abdominal ultrasound (or TDM)in case of abnormal liver function and bone scan if local symptoms.
• Absence of any participation in a clinical trial within 30 days prior to inclusion.
• Absence of any concomitant cancer treatment.
• Absence of any chronic treatment ( ≥3 months) with a daily corticosteroid dose is ≥20mg / day of methylprednisolone or equivalent.
• Hematological function: neutrophils ≥1.5 x 109 / L, platelets ≥100 x 109 / l,hemoglobin ≥10 g / dl (or 6.2 mmol / l).
• Hepatic function: normal total bilirubin; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (LNS)of each center; alkaline phosphatase ≤ 5 x LNS.
• Renal function: serum creatinine ≤ 120 mol / l (1.4 mg / dl); if creatinine > 120 mol / l, creatinine clearance should be ≥ 60 ml / min.
• calculated creatinine clearance (Crockcroft formula) or measured ≥ 60 ml / min
• Estimated life expectancy ≥ 3 months
• Weight loss less than 10% over the last 3 months
• Patient has given its written consent before any specific procedure of the Protocol.
• Women and men of childbearing age should have accepted a medically effectivecontraception during the treatment period and at least 6 months after discontinuationof study treatments (Docetaxel, 5-Fluorouracil and Cisplatin. If pregnancy is declaredby a patient or partner of a patient, it must be followed to know the evolution ofpregnancy.

Exclusion Criteria:

• transglottic T3 with massive infiltration of hemilarynx or T4 with massivecartilaginous tumor lysis or reverse cricoarythénoïdenne region or posteriorhypopharyngeal wall
• tumor requiring the completion of an immediately tracheotomy.
• Tumour available immediately to partial surgery.
• tumor requiring circular hypopharyngectomie
• N3 nodal injury
• Vaccination against yellow fever recent or anticipated
• Deficit known dihydropyrimidine dehydrogenase (DPD)
• Other malignancies within 5 years prior to randomization, with the exception ofadequately treated basal skin cancer and carcinoma in situ of the cervix.
• Patients with AST or ALT> 1.5xULN associated with alkaline phosphatase > 2.5x LNS willnot be eligible for testing.
• symptomatic neuropathy grade ≥2 with NCI-CTC.
• Clinical alteration of hearing function.
• Other concomitant serious medical conditions (partial list):
• Unstable cardiac disease despite treatment.
• Myocardial infarction within 6 months prior to trial entry.
• Neurological or psychiatric history such as dementia, seizures;
• Severe uncontrolled infection.
• Significant gastrointestinal abnormalities, including those that requireparenteral nutrition, active peptic ulcer disease and a history of surgicalprocedures affecting absorption
• Obstructive pulmonary disease requiring hospitalization in the year beforeinclusion.
• Unstable diabetes or other cons-indications to corticosteroids.
• Significant ophthalmologic abnormality.
• Moderate or severe eczema.
• Allergy to iodine.
• Hypersensitivity to Docetaxel, Cisplatin or at one of their excipients.
• Concomitant use of phenytoin, carbamazepine, barbiturates and rifampicin.
• Presence, selection, psychological factors, family, social or geographical may alterpatient compliance with the study protocol and follow-up, a criterion ofnon-inclusion. These factors should be discussed with the patient before inclusion inthe trial.
• Pregnant or nursing women.
• Patient (male or female) of childbearing age not taking adequate contraceptivemeasures.
• Patient deprived of their liberty, without guardianship or curatorship.