Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
This study compare the survival without laryngeal dysfunction 2 years after the end of
 treatment, obtained by chemotherapy followed by radiotherapy or chemotherapy with cisplatin
 administrated during radiotherapy.
In patients with tumors classified as T3 or T4 larynx and hypopharynx, the usually
 recommended treatment was total laryngectomy.This intervention allows to obtain locoregional
 disease control in 75% of cases, without laryngectomy

 TPF arm followed by radiotherapy was validated in a Phase III (GORTEC 2000-01), it will be
 the standard treatment.

 The RTOG study concluded that chemotherapy administrated during radiotherapy became a
 standard of laryngeal preservation.

 Taking together all these considerations, it is necessary to perform a direct comparison in a
 randomized trial to further test this hypothesis. Chemotherapy followed by radiotherapy will
 be the standard arm. It hopes to increase the survival rate from 52% to 65% in the
 experimental arm.
Inclusion Criteria:

 -  Squamous cell carcinoma of the larynx or hypopharynx, histologically proven, locally
 advanced:

 -  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 ≥20
 mg / 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

 -  VHI and DHI questionary

 -  Quality of Life Questionnaire QLQ-C30 and QLQ-H & N35

 -  Patient has given its written consent before any specific procedure of the Protocol.

 -  Women and men of childbearing age should have accepted a medically effective
 contraception during the treatment period and at least 6 months after discontinuation
 of study treatments (Docetaxel, 5-Fluorouracil and Cisplatin. If pregnancy is declared
 by a patient or partner of a patient, it must be followed to know the evolution of
 pregnancy.

 -  Dynamic Vidéoscopie of deglutition

 Exclusion Criteria:

 -  transglottic T3 with massive infiltration of hemilarynx or T4 with massive
 cartilaginous tumor lysis or reverse cricoarythénoïdenne region or posterior
 hypopharyngeal 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 of
 adequately 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 will
 not 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 require
 parenteral nutrition, active peptic ulcer disease and a history of surgical
 procedures affecting absorption

 -  Obstructive pulmonary disease requiring hospitalization in the year before
 inclusion.

 -  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 alter
 patient compliance with the study protocol and follow-up, a criterion of
 non-inclusion. These factors should be discussed with the patient before inclusion in
 the trial.

 -  Pregnant or nursing women.

 -  Patient (male or female) of childbearing age not taking adequate contraceptive
 measures.