Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors

Background. Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase IT study are listed below. Methods. For the phase 11 trial 32 patients (29 male, 3 female) with histologically diagnosed locally advanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The chemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at doses of 20 mg/m(2) and during the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m(2). Results. The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rate is not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrences and six of these patients have in the meantime died. With regards to the four (12%) patients who developed distant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondary malignancies. Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developed grade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant late toxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients. Conclusion. This very aggressive radiochemotherapy protocol yielded excellent response and overall survival rates; however it is associated with a very high rate of acute toxicity. Therefore, in such cases where acute toxicity resulted, extensive supportive care is required.