Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Squamous Cell Carcinoma of Head and Neck
Study type: Interventional
Phase: Phase 2

Summary: 
      The general aim is to compare the cumulative dose of cisplatin administered concomitantly
      with radiotherapy in reference arm A (cisplatin 100 mg / m2 day 1 every 21 days) and in the
      experimental arm B (Cisplatin split 25 mg / m2 / J D1 to D4 all 21 days).
    

Detailed description: 
      The standard treatment for squamous cell carcinoma of the head and neck locally advanced
      non-operated or non-operable is a combination of radiotherapy and concomitant chemotherapy.
      Indeed, the meta-analysis MACH showed for RT / CT associations an absolute survival benefit
      of 8% compared with radiotherapy alone. Cisplatin delivered optimally, ie at a dose of 100 mg
      / m2 on day 1, D22 and D43 of radiotherapy is as effective as combinations of cisplatin and
      5-fluorouracil.

      In post operative, treatment of high risk recurrence forms by Cisplatin, concomitantly with
      radiotherapy, also increases local control and overall survival.

      However, it is an association whose toxicity is significant. The usual limiting toxicities
      were mucositis, dysphagia, nausea and vomiting with malnutrition and biologically kidney
      failure and myelotoxicity. Only 2/3 of the patients receive 3 cycles of cisplatin initially
      programmed.

      As shown in the RTOG 0129 trial, the number of cycles of cisplatin and thus the cumulative
      dose of cisplatin administered concurrently with radiation therapy, significantly influences
      the locoregional control, progression free survival and overall survival.

      One method of reducing the toxicity and thereby, increase the cumulative dose, would be to
      split the administration of cisplatin.

      Moreover, the efficacy of Cisplatin, which only the free fraction is active, seems correlated
      with AUC that peak plasma which would in turn responsible for toxicity. The completion of a
      pharmacokinetic study comparing the AUC and Cmax obtained with cisplatin 100 mg / m2 and
      cisplatin fractionated is essential.

      Finally, the limiting renal toxicity induced by cisplatin is currently diagnosed using the
      creatinine clearance. The Neutrophil gelatinase-associated lipocalin (NGAL) urinary is a new
      diagnosis and prognosis marker of renal impairment following treatment with cisplatin.
      However, further studies are needed to validate its clinical utility.
    

Intervention name(s): Split Cisplatin; Cisplatin; Radiotherapy
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): 25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy.; 100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy.; 70 Gy in 35 fractions of 2 Gy in non-operated patients and 66 Gy in 33 fractions in post-operative.
Other intervention name(s): Cisplatin infusion; Cisplatin infusion; Radiotherapy IMRT with possibly integrated boost
Intervention MeSH terms: Cisplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment