Background: After promising results from TPEx phase II trial in first line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), this trial compared the TPEx regimen (docetaxel-platinum-cetuximab) to the standard EXTREME regimen. Methods: Patients with R/M HNSCC unsuitable for curative treatment were randomized between TPEx (four cycles docetaxel-cisplatin-cetuximab followed by cetuximab maintenance 500 mg/m² every two weeks) and EXTREME (six cycles 5FU-cisplatin-cetuximab followed by weekly cetuximab 250 mg/m² maintenance). Main inclusion criteria were patients fit for cisplatin, performance status (PS) ≤1, creatinine clearance >60ml/min, and age