In a prospective pilot study 21 patients with advanced squamous cell carcinoma of the head and neck were treated with polychemotherapy and Hyaluronidase combined with radiation. With the exception of one patient, who refused laryngectomy, all patients were inoperable. Chemotherapy consisted of 5 mg Vindesine on day 1 and 80 mg/m2 Cisplatin on day 2. 200,000 U Hyaluronidase were given by infusion over 20 min prior to Vindesine and Cisplatin. Radiation in fractions of 2 Gy a day was administered 12 times per cycle (day 3-5, 8-12 and 15-18). Treatment was repeated on day 22 and 43. Total radiation dose was 72 Gy. Side-effects were mainly of local character (moderate severe mucositis in 7, mild mucositis in 14 patients). No severe systemic toxicity was seen. Complete remission was noted in 17 out of 21 patients. 16 patients are now a life without progression. 1 patient in complete remission died 5 months after therapy due to pneumonia without evidence of tumor. The mean time of follow up is 16 months (range 3-42). The preliminary results suggest that combined therapy with Vindesine, Cisplatin, Hyaluronidase and Radiation is well tolerable and highly effective against advanced squamous cell carcinoma of the head and neck.